POSTED: 4 Nov 2026

What Do Clinical Studies Actually Show About Tretinoin for Wrinkles & Skin Ageing?

Tretinoin is often described as the gold standard of anti-ageing skincare with decades of clinical trials behind it. Researchers have been testing tretinoin against plain cream in people with sun-damaged skin since the 1980s. These studies consistently show that it softens fine wrinkles, smooths rough skin and increases collagen production. They also show that a low strength can work as well as a high one and that results can be maintained with only a few applications a week. However, it is not a silver bullet and like any topical treatment has its limits. So how well does tretinoin work for wrinkles and what can you realistically expect? In this article, we’ll explore what the trials show and critique the evidence around its effects on wrinkles and collagen production as well as how it compares with retinol.

When Was Tretinoin First Found to Help Wrinkles?

The first simple clinical trial on tretinoin and skin ageing was in 1986 in people with sun-damaged skin. This study was around 15 years after tretinoin came into use as an acne treatment. The dermatologist Albert Kligman, who had helped to develop tretinoin for acne in the late 1960s, compared 0.05% tretinoin cream with its vehicle (the same cream without tretinoin) on the faces and forearms of people with photoaged skin. Examination of the treated skin under a microscope showed it had a thicker outer layer with fewer abnormal cells. His conclusion from this data was that tretinoin could at least partly reverse structural damage due to years of sun exposure.

A double-blind higher level trial followed in 1988. Published in JAMA, it involved 30 people who used 0.1% tretinoin or the vehicle for 16 weeks. Fourteen of the 15 people who applied tretinoin to their face improved, whereas none of those using the vehicle did. This small study set the stage for the larger trials in the 1990s into tretinoin for wrinkles and skin ageing.

Does Tretinoin Work for Wrinkles?

Yes, tretinoin improves fine wrinkles caused by sun damage. This is supported by randomised controlled trials going back almost 40 years. In one of the best known, 251 people with mild to moderate sun damage applied either a tretinoin cream or the vehicle every day. After 24 weeks, 79% of those using 0.05% tretinoin had improvement in photo-aged skin compared with 48% of those using just the vehicle.

What is also interesting about this study is that almost half of the people who used a plain cream (vehicle) experienced improvement too. This might be because everyone who joins a trial like this tends to look after their skin more carefully, which includes moisturising and staying out of the sun. If that is the case, it means that the benefit which belongs to tretinoin by itself is probably more like 31%. It also reinforces the importance of a good skincare routine in and of itself.

The wider evidence also supports these earlier studies. A 2025 meta-analysis pooled eight randomised trials involving 1,361 people and found that tretinoin improved both fine and coarse wrinkles more than the vehicle did. Its authors concluded that tretinoin is a safe and effective treatment for wrinkles caused by sun damage. It is important to highlight that most of these studies were on people with photoaged skin which is skin with visible damage from years of sun exposure.

StudyWhat was testedWhat it foundWorth knowing
Weiss 19880.1% tretinoin against vehicle for 16 weeks in 30 people14 of 15 faces improved with tretinoin and none with vehicleThe first double-blind trial, and a small one
Weinstein 19910.05% or 0.01% tretinoin against vehicle for 24 weeks in 251 people79% improved on 0.05% tretinoin and 48% on vehicleAlmost half improved with a plain cream
Renova label trials0.02% tretinoin against vehicle for 24 weeks in 656 people across five trialsIn four of the trials, 60% improved on tretinoin and 39% on vehicleTwo of the five trials met the regulator’s standard
Griffiths 19950.025% and 0.1% tretinoin against vehicle for 48 weeks in 99 peopleBoth strengths worked equally well0.1% caused more irritation
Kang 20050.05% tretinoin against vehicle for up to two years in 204 peopleFine and coarse wrinkles improved more with tretinoinThe longest controlled trial so far
Griffiths 19930.1% tretinoin against vehicle for 10 to 12 months in 29 peopleCollagen formation rose by 80% with tretinoinSmall study using forearm skin
Olsen 1997Three times a week, once a week or no tretinoin in 126 people who had finished 48 weeks of daily useThree times a week maintained resultsEveryone had completed a year of daily use first
Chien 2022A 1.1% retinol blend against 0.02% tretinoin for 24 weeks in 20 womenNo significant differenceToo small to prove they’re equal
Huang 2025Pooled analysis of eight trials and 1,361 peopleFine and coarse wrinkles both improvedSigns of publication bias

How Much Difference Does Tretinoin Make to Wrinkles?

So we know that tretinoin can help treat wrinkles but the question that remains is by how much? Tretinoin made a visible difference to fine wrinkles for most people in the trials and for some the improvement was substantial. The clearest numbers come from the US prescribing information for Renova, which is a 0.02% tretinoin cream that has regulator approval for fine facial wrinkles. In four trials involving 559 people, doctors scored fine wrinkles on a 10 point scale before treatment and again after 24 weeks.

Change in fine wrinkles after 24 weeksTretinoin 0.02%Vehicle
Worse1%3%
No change40%58%
Minimal improvement (one point)35%27%
Mild improvement (two points)15%9%
Moderate improvement (three points or more)10%3%

The data showed that six out of every ten people who used tretinoin for six months saw their fine wrinkles improve, compared with four out of ten who used the plain cream. Tretinoin also roughly tripled the chance of a moderate improvement. These results came from a low 0.02% strength. Everyone in the trials followed a routine of sunscreen, sun avoidance and moisturiser as well.

Tretinoin does not eliminate wrinkles or reverse photoageing but putting the evidence together, it is realistic to expect softer fine lines and smoother skin. Deeper lines can respond too based on data from a two year trial and meta-analysis on 0.05% tretinoin. However, the Renova trials didn’t show a clear effect on coarse wrinkles, skin laxity or mottled hyperpigmentation at the lower 0.02% strength.

Does Tretinoin Increase Collagen?

There is evidence that tretinoin can increase collagen production in sun-damaged skin. The key study on this was published in the New England Journal of Medicine in 1993. The researchers first showed that sun-damaged forearm skin was forming 56% less collagen type I than skin which had been protected from the sun. They then treated 29 people with either 0.1% tretinoin or the vehicle for 10 to 12 months. Collagen type I formation rose by 80% in the tretinoin group and fell by 14% in the vehicle group.

A later two year trial supported it, as a marker of collagen production rose in facial skin after 12 months of treatment. Tretinoin also appears to protect the collagen you already have. In a laboratory study of human skin, applying tretinoin before UV exposure reduced the enzymes that break down collagen by 70 to 80%.

Although these studies are promising, it is important to note that there are some limitations. Firstly, the 1993 study tested it on forearms rather than faces. This limits interpretation as skin on the face differs in terms of thickness, skincare as well as UV exposure. Both studies also used skin biopsies to analyse effect of tretinoin on collagen. The reason this requires caution is that a rise in collagen formation isn’t the same as a measure of how much younger someone looks. So although the findings give a convincing explanation for why fine wrinkles improve, they don’t show that tretinoin restores lost volume or lifts sagging skin because they did not look at this.

What Strength of Tretinoin is Best for Wrinkles?

You don’t need a high strength of tretinoin to treat wrinkles. The one trial that compared a low and a high strength directly found that both worked equally well. In that study, 99 people used 0.025% tretinoin, 0.1% tretinoin or the vehicle once a day for 48 weeks. Both strengths improved photoageing compared with the vehicle and there was no significant difference between them. The 0.1% cream did cause more redness and scaling.

This is good news if your skin is sensitive. It means that lower strength tretinoin can be effective for wrinkles. The effectiveness of lower strengths is also backed by the Renova trials which used 0.02% and several of the larger trials which used 0.05%. The main limitation of these results is they come from relatively small studies each testing only one type of formulation and a small number of strengths. They don’t automatically extrapolate to a different cream base, gel or in between strengths. In practice, the most useful tretinoin strength is usually the one that your skin can tolerate frequently and consistently.

How Long Does Tretinoin Take to Work on Wrinkles?

Tretinoin takes around three to six months to start to improve the appearance of fine wrinkles. The main trials measured their results at 24 weeks. The Renova label advises that up to six months of treatment may be necessary before you can see effects. In the two year trial, the tretinoin group was still doing better than the vehicle group at the end of the study. This shows that the benefit is sustainable with continued use. How long tretinoin takes to work also varies with the condition of your skin, health, lifestyle and overall skincare habits.

What Happens if You Stop Using Tretinoin?

You can maintain your results with tretinoin by using it a few nights a week, although some of the improvement fades if you stop completely. In one study, 126 people who had finished 48 weeks of daily 0.05% tretinoin went on to use it three times a week, once a week or not at all for a further 24 weeks. Three times a week maintained the improvement, once a week maintained it less well and those who stopped lost some of their results. The Renova label warns that some of the benefit may be lost around 12 weeks after stopping. Research supports long term use at a frequency that your skin tolerates, which is often lower than people expect and is the thinking behind tretinoin microdosing.

Does Tretinoin Work for Wrinkles on Darker Skin Tones?

Tretinoin is used across all skin tones, but the wrinkle trials can’t yet tell us how well it works on darker skin. This is because most of them were carried out in women with lighter skin tones. The Renova programme included one trial of 107 people with darker skin. In that study, 43% of the vehicle group had a minimal or mild improvement in fine wrinkles compared with 29% of the tretinoin group. However, this may reflect the small size of people with darker skin tones in the study rather than tretinoin working less in this group. A 2026 study from India reported improvements in wrinkles and skin texture after 16 weeks of 0.1% tretinoin in 40 people. Unfortunately, it had no comparison group, so we can’t tell how much of the change was due to tretinoin itself.

There is definitely a huge gap in this area of research regarding the effect of tretinoin on different skin tones. It is a shame and data is necessary to not only look at the effect of tretinoin on darker skin tones but also best use and strengths as people with darker skin tones are more prone to hyperpigmentation after irritation. In the absence of this data, it is best to start on low strengths and frequencies of tretinoin in people with darker skin to avoid irritation, hyperpigmentation or burns.

Is Tretinoin Better Than Retinol for Wrinkles?

There is far more clinical trial evidence behind tretinoin for wrinkles than retinol. However, few studies compare them head to head so the research doesn’t tell us how much better it is. We know that retinol requires conversion into tretinoin within the skin before it can work. This is why most scientists and clinicians regard it as the gentler and weaker of the two.

The most direct comparison is a 2022 trial which tested a cosmetic cream containing 1.1% retinol and retinol esters against 0.02% tretinoin for 24 weeks. There was no significant difference in photoageing scores between the two, and the retinol cream caused less redness. However, the study only looked at 20 people and all of them were white women. Another major limitation is that this study was funded by the company that makes the retinol product. Furthermore, they did not compare apples with apples. The retinol product was around 50 times more concentrated than the tretinoin strength it was compared with. Given the problematic design of this trial, there is no evidence to support superiority of retinol over tretinoin.

However, retinol does have evidence to support its use for wrinkles. For instance, in a study of 36 people with an average age of 87, a 0.4% retinol lotion improved fine wrinkles on the upper inner arm compared with the vehicle over 24 weeks. Although tretinoin is often described as being 20 times stronger than retinol, we couldn’t find a clinical trial to support a fixed correlation between strengths and clinical effects. So whilst equivalent retinol strengths are useful in terms of thinking about potential side effects, they are not a direct measure of how much more your wrinkles will improve.

Can Tretinoin Prevent Wrinkles?

Tretinoin may help prevent wrinkles because it increases collagen but there is no clinical trial that has specifically tested this. However, the treatment trials enrolled people who already had visible sun damage and the longest controlled study lasted two years. This means that they can’t tell us what happens when someone starts in their twenties and continues for decades.

Incidentally, the best evidence for preventing wrinkles still belongs to the humble sunscreen. In an Australian randomised clinical trial of 903 adults under 55, those who applied sunscreen every day showed no detectable increase in skin ageing after four and a half years. They also had 24% less skin ageing than those who used sunscreen only when they chose to. However, they measured skin ageing on the backs of the hands rather than the face. Based on this and the vehicle data, the best way to use tretinoin is alongside a good moisturiser and on top of daily sun protection.

What are the Side Effects of Tretinoin?

Irritation is the main side effect of tretinoin. In the Renova trials of 0.02% tretinoin for wrinkles, nearly all participants reported at least one reaction such as dryness, peeling, burning, stinging, redness or itching. For 32% of them the irritation was severe leading to a pause in treatment or requiring use of a mild steroid cream. About 4% had to stop tretinoin altogether. These reactions tend to occur early in treatment and ease as the skin adjusts. You can reduce them by starting slowly and supporting your skin barrier with a plain moisturiser. Protocol also matters! Using more than a small pea-sized amount will neither work faster nor better and just increases the risk of irritation.

Tretinoin also makes your skin more likely to burn, so daily sunscreen is part of the treatment. In the UK, the MHRA advises that topical retinoids shouldn’t be used during pregnancy or when planning a pregnancy. Most prescribers also recommend the same precaution during breastfeeding.

ClaimEvidenceVerdict
Tretinoin improves fine wrinklesStrongTrue. In the Renova trials, 60% improved with tretinoin and 39% with a plain cream.
Tretinoin boosts collagenStrongTrue. Collagen formation rose by 80% in biopsies, although this doesn’t restore lost volume.
A low strength works for wrinklesStrongTrue. In the only direct comparison, 0.025% matched 0.1% with less irritation.
Tretinoin improves deep wrinklesMixedSometimes. The two year trial found a benefit, whereas the 0.02% trials did not.
You can maintain results with less frequent useEarlyTrue in one trial. Three nights a week maintained results after a year of daily use.
Tretinoin works the same on all skin tonesEarlyUnknown. The one controlled trial in darker skin was small, so more research is needed.
Tretinoin is 20 times stronger than retinolWeakUnproven. One small trial found no difference between a retinol blend and tretinoin.
Starting tretinoin young prevents wrinklesNonePlausible but untested. The trial evidence for prevention belongs to daily sunscreen.
Tretinoin erases wrinklesNoneFalse. It softens fine wrinkles but does not remove them.

Should You Use Tretinoin for Wrinkles?

Tretinoin is a reasonable treatment if your main concern is fine lines and rough or uneven skin from sun damage and you’re prepared to use it consistently for at least six months. It is however a prescription only medicine and is not effective or safe for everyone. There are also a number of basic considerations for those looking to use tretinoin for wrinkles:

  • Expectations: Aim for softer fine lines and smoother texture. Deep folds, sagging and volume loss are usually more responsive to in-clinic options such as anti-wrinkle injections, fillers or lasers.
  • Sunscreen: Apply a broad spectrum sunscreen every morning. Every trial participant had to protect their skin from the sun so the results depend on it.
  • Strength: Start low. A low strength was as effective as a high one in the trial that compared them, so there’s no need to rush upwards and risk damaging your skin barrier.
  • Frequency: Build up gradually and follow your prescriber’s advice on how to use tretinoin. Persistent or severe irritation is a reason to ask for advice and not something to push through.
  • Delicate areas: Take extra care around the eyes and mouth, where irritation is more likely. Using tretinoin under the eyes needs a gentler approach under the guidance of your prescriber.
  • Time: Judge your results after six months. Photos taken in the same light with a relaxed face are more reliable than memory.

In the UK, tretinoin is a prescription only medicine. Using it for skin ageing is generally an off-label use, which means it should follow an assessment by a prescriber who can explain the likely benefits and side effects for your skin. It is also not the only retinoid or anti-ageing treatment. There are many other options. These include other prescription retinoids such as adapalene and tazarotene, over the counter retinol and a retinoid-free routine built around ingredients like peptides. This is why it is important to tailor any treatment to your skin, health and individual needs. If you’re comparing telederm clinics, our reviews of where to get tretinoin online in the UK and anti-ageing treatments online explain how the different services work.

Tretinoin has been studied for wrinkles for almost 40 years and the evidence has held up well. Randomised trials show that it softens fine wrinkles, smooths sun-damaged skin and increases collagen production. They also show that a low strength is enough for most people and that a few nights a week can maintain the results. The improvement is gradual, so it helps to expect softer lines over six months as opposed to wrinkles disappearing. Crucially, always remember to pair tretinoin with daily sun protection. Irritation is common in the early weeks but it can usually be managed by starting slowly and at low strengths. Lastly, tretinoin is not the only option and is not suitable for everyone. There are many skin ageing treatments and the right one depends on your individual needs and skin health.

At City Skin Clinic, we are passionate about personalised skincare. Our online clinic provides topical skincare. Where appropriate, our doctors design custom treatments for skin ageing, hyperpigmentation, melasma and acne using ingredients such as tretinoin, azelaic acid and hydroquinone. To start, book a virtual video consultation or use our online consultation form. The journey towards great skin starts here.

This article is intended for general informational purposes only and is not a substitute for medical advice, diagnosis or treatment. Always consult a qualified medical provider for any medical concerns or questions you might have.

Authored by:

Dr Amel Ibrahim
Aesthetic Doctor & Medical Director
BSC (HONS) MBBS MRCS PHD
Founder City Skin Clinic
Member of the Royal College of Surgeons of England
Associate Member of British Association of Body Sculpting GMC Registered - 7049611

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