Comparing Adapalene vs. Tretinoin

If you or a loved one struggle with acne, you’re probably familiar with the frustration of spending time and money on various over-the-counter (OTC) acne treatments that rarely seem to work.

Fortunately, some people have seen clearer skin using Differin (adapalene).

Differin is similar to tretinoin, a prescription retinoid. These two medications lessen the severity of existing acne and assist in the healing of developing pimples.

However, while similar, these two topically applied drugs contain some significant differences that potential consumers should be aware of, such as potency and available dosing volumes.

You can read on to learn more about adapalene versus tretinoin to see which option might be better for you.

Comparing Adapalene vs. Tretinoin
Getty Images / Boyloso.

Adapalene vs. Tretinoin: Uses

Adapalene and tretinoin are topical medications that you apply directly to the skin.

Both medicines are retinoids, a class of compounds similar to vitamin A. Besides the topical treatment of acne, retinoids can be prescribed in oral form to treat severe acne and other medical conditions, such as psoriasis or leukemia.

Adapalene

Adapalene (brand names: Differin, Differin-OTC) is a topical medication. The Food and Drug Administration (FDA) has approved adapalene to treat acne in people 12 and older.

Adapalene is sometimes used off-label (a non-FDA-approved use) to treat other skin conditions, such as:

Tretinoin

Tretinoin (brand name: Retin-A) is FDA-approved to treat acne vulgaris (the medical term for acne).

It is also used off-label for other skin conditions, such as facial wrinkles, keratosis pilarisactinic keratosis, and dark spots.

Other brand-name prescription drugs contain tretinoin as an active ingredient. For example, Renova is a prescription cream that contains tretinoin 0.2%.

Renova is FDA-approved for managing facial wrinkles as part of a complete skincare program that includes regular sunscreen use and limiting sunlight exposure.

Another example is Tri-Luma, a prescription cream that combines tretinoin 0.05% with a steroid (fluocinolone) and a skin-lightening agent (hydroquinone).

Tri-Luma cream is FDA-approved to treat melasma, a condition that causes dark patches on your face.

Adapalene vs. Tretinoin: What’s the Difference?

One of the main differences between adapalene and tretinoin is OTC versus prescription (Rx) status.

Of the two, only adapalene is available without a prescription as Differin-OTC. It comes as a 0.1% gel.

A higher strength of adapalene gel (0.3%) and other topical forms of the drug are available by prescription.

In contrast, tretinoin is not available in an OTC version. Retin-A and all other medications containing tretinoin require a prescription from a healthcare provider.

The other main difference is that tretinoin is generally more potent—and thus might cause more side effects—than adapalene. Studies have found that tretinoin causes more skin irritation than adapalene.

Researchers conducted a study involving 150 people to compare the effectiveness of adapalene 0.1% gel and tretinoin 0.025% gel for treating acne.

The results revealed that both options effectively reduced acne, but adapalene caused less irritation than tretinoin.

Dosage Differences

Adapalene and tretinoin are typically applied once daily, usually before bedtime.

When you first start using either drug, your healthcare provider will likely recommend starting with the lowest strength.

They may also suggest only applying the product every other day to help minimize initial side effects. 

Be sure to follow the directions on the product labeling or from your healthcare provider.

The table below summarizes the forms and strengths of adapalene vs. tretinoin:

Active Ingredient (Brand names): Forms and strengths available:
● Adapalene (Differin, Differin-OTC) OTC: ● Gel: 0.1%   Rx-only: ● Gel: 0.3% ● Cream: 0.1% ● Lotion: 0.1% ● Solution/swab: 0.1%
● Tretinoin (Retin-A, Retin-A Micro, Atralin, Altreno, Renova, Avita) Rx-only: ● Gel: 0.01%, 0.025%, 0.04%, 0.05%, 0.06%, 0.08%, 0.1% ● Cream: 0.02%, 0.025%, 0.05%, 0.1% ● Lotion: 0.05% 

Which Is More Effective?

According to the most recent clinical trials that have compared adapalene and tretinoin for acne, most research has concluded that tretinoin has more excellent anti‐acne effects than adapalene.

However, tretinoin also has a higher chance of causing skin irritation. 

Acne: One study compared the effectiveness and safety of adapalene and tretinoin for treating acne. While tretinoin was more effective in non-inflammatory, severe acne, tretinoin and adapalene were generally equally effective for inflammatory acne.

This same study found that adapalene was better tolerated and produced fewer side effects.

However, a review of three comparative trials concluded that adapalene was more effective than tretinoin for treating acne.

Photoaging: A different study compared adapalene vs. tretinoin for wrinklesdark spots, and rough patches in sun-damaged skin. This study found that adapalene gel was equally effective as tretinoin cream in improving skin appearance.

Knowing which medication is better for you may take trial-and-error, though evidence points to adapalene causing fewer side effects.

Since everyone's skin is unique, consult a dermatologist or healthcare provider for personalized advice.

What Are the Side Effects?

Overall, the side effects of adapalene and tretinoin are similar.

Both drugs commonly cause skin irritation, especially within the first two weeks of treatment.

Common Side Effects

The following more common, less severe side effects associated with using adapalene or tretinoin include:

While both medications are relatively safe, results will vary from person to person. In comparison, more severe side effects are typically seen with tretinoin.

If you are experiencing side effects with tretinoin cream, you might have better luck and fewer side effects if you try the micronized gel form instead, Retin-A Micro.

Severe Side Effects

While more rare, severe side effects of adapalene or tretinoin may include:

  • Lip swelling
  • Excessive skin redness at the area of application

Contact a trusted healthcare professional if you experience severe side effects with either medication, such as painful burning, itching, irritation, redness, or an allergic reaction.

Adapalene vs. Tretinoin: Which One to Use

Adapalene and tretinoin are similar medications with comparable effectiveness and safety. Adapalene has been shown to cause fewer side effects than tretinoin, leading some people to choose this option over tretinoin.

However, tretinoin takes a shorter time to reach its full effect in treating acne. Adapalene may take eight to 12 weeks to see acne improvement, while tretinoin only takes around six weeks.

Both medications have been shown to have similar efficacy for wrinkles and aging skin.

When you start using either adapalene or tretinoin, your acne may get worse before it gets better.

Adapalene may worsen your acne for the first three weeks, but complete improvement can take eight to 12 weeks. Tretinoin may worsen acne by causing redness, scaling, and pimples for the first seven to 10 days of treatment.

However, you will typically see improvement in acne within two to three weeks of starting tretinoin, though it can take up to six weeks in some cases.

You can switch between adapalene and tretinoin if you find that one medication isn't working for you and want to try another, though since both drugs are retinoids and work in the same way, you should not use both at the same time.

To try tretinoin, you must consult a healthcare provider for a prescription. 

Interactions

The ingredients in certain skincare products may interact with either adapalene or tretinoin.

Adapalene and tretinoin often cause dryness, and various chemicals in products and makeup may cause your skin to become even drier.

This is a vicious cycle since dry skin is even more prone to irritation from adapalene or tretinoin.

If using either medication, it is best to avoid other topical products containing the following ingredients:

Consult a pharmacist or healthcare provider before using either product if you are pregnant, breastfeeding, or have medical conditions. 

Summary

While both acne medications have similar efficacy, adapalene tends to be better tolerated with less skin irritation than tretinoin.

Both drugs are commonly used off-label for anti-aging benefits. Tretinoin is only available with a prescription, but you can purchase adapalene gel OTC as Differin-OTC.

Other forms and higher strength of Differin are prescription-only. 

Frequently Asked Questions

  • Is there a cost difference between adapalene and tretinoin?

    OTC drugs are generally less expensive than most prescription drugs. Pricing of Differin-OTC, for example, depends on the retailer. This product is available at most pharmacies, grocery stores, big box stores, and online retailers.

    What you pay for prescription versions of adapalene and tretinoin may depend on your insurance coverage and whether you use manufacturer coupons or pharmacy discount programs. 

  • Are there any similar medications to adapalene and tretinoin?

    Other topical retinoids are similar medications to adapalene and tretinoin. Other medicines prescribed for treating acne include Tazorac (tazarotene), Aklief (trifarotene), Epiduo (adapalenel; benzoyl), and Arazlo (tazarotene).

    Oral acne medications are a better option for some, while some individuals have success with a combination of both. Talk to your healthcare provider to see which would be best for you.

19 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
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Patricia Weiser, Updated Headshot

By Patricia Weiser, PharmD
Patricia Weiser, PharmD, is a licensed pharmacist and freelance medical writer. She has more than 14 years of professional experience.