Adapalene (Differin) for Acne: How It Works and How to Use It

Adapalene is a topical retinoid, and at 0.1% it’s the only retinoid you can buy for acne in the US without a prescription (Differin is the original brand). It works by keeping pores from clogging in the first place, which makes it useful for blackheads, whiteheads and pimples alike. Evidence for it is solid by acne standards, but it takes up to 3 months to work, often irritates at first, and is generally avoided during pregnancy.

What is adapalene?

Adapalene is a synthetic retinoid, a vitamin A-derived drug. It was originally approved in 1996 as a prescription product. On July 8, 2016, the FDA approved adapalene 0.1% gel for over-the-counter use in people 12 and older. FDA noted it was the first retinoid made available OTC for acne and the first new OTC active ingredient for acne since the 1980s.

According to StatPearls, adapalene now comes as a 0.1% gel (OTC), 0.1% cream and lotion and a 0.3% gel (prescription), and in prescription combinations with benzoyl peroxide. Several generic OTC 0.1% gels are now sold alongside the original brand; the active ingredient is the same.

Adapalene is not the same as retinol, the cosmetic retinoid in many anti-aging serums. The AAD’s retinoid vs retinol explainer describes retinol as one type of retinoid used mainly for tone and texture. Adapalene is a regulated acne drug. More on the difference in retinol vs retinoids.

How does adapalene work?

Retinoids tackle the very first stage of acne: the microcomedo, a microscopic plug of skin cells and oil. StatPearls explains that adapalene binds to specific retinoic acid receptors in the skin (RAR-beta and RAR-gamma) and “normalizes the differentiation of follicular epithelial cells to prevent microcomedone formation.” It also dampens some inflammatory pathways, which helps with red spots.

Because it works on prevention, adapalene is meant to be applied to the whole area where you break out, not dabbed on individual spots. The OTC label says to cover the entire affected area with a thin layer once a day.

What does the evidence show?

The 2024 American Academy of Dermatology (AAD) guideline strongly recommends topical retinoids for acne; MDedge’s guideline coverage reports that this strong recommendation is based on moderate-certainty evidence. The AAD’s patient pages recommend adapalene for blackheads, whiteheads and pimples. In the UK, the NICE-based pathway summarized by NHS Scotland lists a fixed combination of adapalene and benzoyl peroxide as a first-line option for acne of any severity.

Put together: adapalene 0.1% beats an inactive gel, performs about as well as older tretinoin with less irritation, and works best combined with benzoyl peroxide. The 0.3% prescription strength is somewhat more effective, which is worth knowing if the OTC version plateaus.

Adapalene vs benzoyl peroxide and salicylic acid

The three main drugstore acne actives work in different ways. Adapalene normalizes how skin cells shed inside the follicle so plugs don’t form. Benzoyl peroxide is bactericidal against Cutibacterium acnes. Salicylic acid is an oil-soluble exfoliant that loosens existing plugs.

Head to head, adapalene and benzoyl peroxide seem roughly comparable: the 2020 Cochrane review found there may be little to no difference in participant-reported improvement between them, although that evidence is low certainty. Both carry strong recommendations in the 2024 AAD guideline, whereas salicylic acid gets a conditional one. The bigger gains come from combining them. In the 2021 network meta-analysis, 54% of people using adapalene plus benzoyl peroxide reported improvement, compared with 35% on benzoyl peroxide alone, with slightly more people stopping the combination because of side effects.

So if you’re choosing just one, adapalene is a strong pick for clogged pores and mixed acne, and benzoyl peroxide is a strong pick for inflamed spots. If one alone isn’t enough after a few months, using both (introduced gradually) is the combination with the best evidence. For the salicylic acid side of the comparison, see salicylic acid for acne.

How to use adapalene

These steps follow the OTC Drug Facts label unless noted:

1. Once a day, no more. Adults and children 12 and older use it once daily; the label says not to use it more than once a day.
2. Clean and dry first. Wash gently and pat dry, then apply a thin layer over the entire affected area.
3. Ease in if you’re sensitive. The AAD’s advice for retinoids is to use the least-intense formula at night, every other night to start, and slowly build up.
4. Moisturize and wear sunscreen daily. The label says to limit sun exposure, including tanning beds, and use sunscreen.
5. Expect a rough start. The label warns that in the early weeks your acne may appear to worsen before it improves, and that it may take up to 3 months of daily use to see results.

I’ve written a fuller walkthrough in how to start adapalene, including how to layer it with benzoyl peroxide.

Side effects and precautions

FDA lists the common adverse reactions as redness, scaling, dryness, itching and burning or stinging. The OTC label says irritation is more likely in the first few weeks. It also warns:

• Don’t use it on damaged skin (cuts, abrasions, eczema or sunburn).
• Don’t wax to remove hair in areas where you’ve applied it.

Adapalene tends to be gentler than older retinoids. StatPearls reports discontinuation rates due to side effects of roughly 1.3% for adapalene versus 2.4% for tretinoin in comparative trials. It’s still worth introducing slowly, and if you’re also starting benzoyl peroxide, adding one product at a time makes it easier to tell what’s irritating you.

Can you use adapalene while pregnant or breastfeeding?

This is the big caveat. Oral retinoids (like isotretinoin) cause birth defects, and although very little topical adapalene is absorbed, the usual advice is to avoid it in pregnancy:

• The AAD says most experts recommend stopping topical retinoids during pregnancy.
• MotherToBaby says it has generally been recommended to avoid topical retinoids such as tretinoin and adapalene in pregnancy, while noting only small amounts are likely to be absorbed.
• The NHS says topical retinoids are not suitable for use during pregnancy.
• The OTC label says to ask a doctor before use if you are pregnant or breastfeeding.

For breastfeeding, the NIH’s LactMed database says topical adapalene hasn’t been studied, but because it’s poorly absorbed it is “probably a low risk to the nursing infant,” as long as it’s kept off the nipple area and away from the baby’s skin. If you’re pregnant or planning to be, ask your clinician about options such as azelaic acid; see azelaic acid for acne.

Frequently asked questions