Azelaic acid and tretinoin: how they compare

Azelaic acid and tretinoin are two prescription acne creams that trials have compared head to head and that dermatologists have also used together. In a 1989 trial, azelaic acid 20% cream cleared clogged pores as well as tretinoin 0.05% cream and caused fewer skin side effects. A 2000 paper reported that azelaic acid worked better when combined with tretinoin. The labels add one caution: the tretinoin label asks for care with any other product applied to the skin. This guide compares the two, sets out what the studies found when they were combined, and explains how prescribers schedule them. For the ingredient itself, see what azelaic acid is. For retinol and adapalene, see azelaic acid with retinol.

How they compare

	Azelaic acid	Tretinoin
What it is	A dicarboxylic acid found in grains and made by the body	A retinoid, a medicine made from vitamin A
FDA-approved for	Acne (20% cream); rosacea bumps (15% gel and foam)	Acne
How often, per label	Twice a day	Once a day, at bedtime
Common early reactions	Stinging, burning, itching	Redness, peeling; acne may look worse at first
Sun	No reactions to light in the gel's safety studies	The label says to keep sun exposure to a minimum
Pregnancy, per the AAD	"Thought to be safe"	"Most experts recommend stopping"
Dark marks	The AAD says it treats dark spots after acne	The AAD says a retinoid can help lighten dark spots after acne

The tretinoin label says tretinoin is "indicated for topical application in the treatment of acne vulgaris." Its directions: "once a day, before retiring, to the skin where acne lesions appear, using enough to cover the entire affected area lightly."

Each label describes how its medicine is thought to work. The tretinoin label says it "decreases cohesiveness of follicular epithelial cells with decreased microcomedo formation," which means it loosens the cells lining the pore so fewer tiny plugs form, and that it speeds the turnover of those cells, "causing extrusion of the comedones." The azelaic acid 20% cream label says it acts against acne bacteria and helps skin cells inside the pore shed normally. Both labels say the exact way their medicine works is not fully known.

How they did head to head

For acne. The 1989 paper in Acta Dermato-Venereologica compared azelaic acid 20% cream with tretinoin 0.05% cream in 289 people with acne made mostly of clogged pores, over 6 months. Azelaic acid "was equally effective as 0.05% tretinoin cream in reducing the number of comedones and with respect to overall response," and it "was better tolerated, causing fewer local side effects." A 2020 Cochrane review, which pools trials and grades how far the results can be trusted, rated that comparison as moderate-quality evidence of "probably little or no difference."

On clogged pores under the microscope. A 2024 review in Clinical, Cosmetic and Investigational Dermatology describes a study of 30 people who used azelaic acid 20% cream twice a day, tretinoin 0.05% cream once a day, or a plain cream. Both medicines reduced clogged pores, and "the reduction in follicular hyperkeratinization induced by AZA was similar to that induced by RA." In plain words, azelaic acid reduced the plugging of pores to a similar degree as tretinoin.

Against a mix with glycolic acid. A 1998 trial in Clinical Therapeutics compared azelaic acid 20% cream plus a glycolic acid lotion with tretinoin 0.025% cream for 12 weeks. The azelaic acid pair reduced red bumps more and, as rated by doctors, caused less dryness, scaling and redness.

The 2024 acne guideline from the American Academy of Dermatology (AAD) still ranks the two differently. It gives topical retinoids, which include tretinoin, a strong recommendation, and azelaic acid a conditional one.

What happened when they were combined

• A 2000 paper in the Journal of the American Academy of Dermatology reported that azelaic acid's effect "can be enhanced, and patient ratings of overall impression improved, when it is used in combination with other topical medications," including "tretinoin 0.025% cream."
• A 2020 case series described four women whose chest and back acne was "successfully treated with a combination of tretinoin lotion 0.05% and azelaic acid 15% foam." A case series follows a few patients with no comparison group.
• For melasma, the 2024 review describes a study of azelaic acid 20% with tretinoin 0.05% cream applied nightly for 12 weeks. It found "some effectiveness" along with "notable adverse reactions."

These studies show the pair has been used under medical care. None is a large trial of the two together against each alone.

What the labels say about combining

The tretinoin label is cautious about anything else on the skin: "Concomitant topical medication, medicated or abrasive soaps and cleansers, soaps and cosmetics that have a strong drying effect, and products with high concentrations of alcohol, astringents, spices or lime should be used with caution because of possible interaction with tretinoin." It names "sulfur, resorcinol, or salicylic acid" as needing particular caution. It also tells patients not to use other medicines with it unless their doctor recommends them.

MedlinePlus says people using tretinoin should not use "any other topical medications, especially benzoyl peroxide, hair removers, salicylic acid (wart remover), and dandruff shampoos containing sulfur or resorcinol unless your doctor directs you to do so."

The azelaic acid labels have no drug interaction section. They ask users to avoid "alcoholic cleansers, tinctures and astringents, abrasives and peeling agents."

So the combination is a prescriber's decision. If a doctor gave you tretinoin, ask that doctor before you add azelaic acid.

How the two are scheduled

No source Skinli read sets a standard schedule for the pair. The common patterns are:

• Morning and night. Tretinoin at bedtime, as its label directs, and azelaic acid in the morning. Skinli's 12-week plan uses this pattern with the retinoid adapalene: azelaic acid 10% cream in the morning from week 5, and the acne gels at night.
• Same night, both products. The 2000 paper and the case series used them together. Ask your prescriber about order and waiting time.
• Alternate days. No study Skinli found tested this pattern. Ask your prescriber before trying it.

Whichever pattern you use, the tretinoin label says excess product brings no faster result: "If medication is applied excessively, no more rapid or better results will be obtained and marked redness, peeling, or discomfort may occur."

Irritation

Both products irritate at first, in different ways. The tretinoin label says "during the early weeks of therapy, an apparent exacerbation of inflammatory lesions may occur," and MedlinePlus says acne "probably will get worse (red, scaling skin and an increase in acne sores) during the first 7 to 10 days." The azelaic acid 15% gel label reports burning, stinging or tingling in 29% of users, usually in the first few weeks. Starting both at once makes it hard to tell which one caused a reaction. The purging guide compares the early weeks of each.

Both labels also mention skin color. The tretinoin label reports "temporary hyper- or hypopigmentation," meaning darker or lighter patches, with repeated use. The azelaic acid labels report isolated cases of lighter patches and ask people with darker skin to watch for early signs.

When azelaic acid is used instead

NICE, which writes acne guidance for the NHS in England, recommends topical azelaic acid with an antibiotic pill for moderate to severe acne. Its reasoning: "It was therefore considered to be a good alternative for people who have irritation to topical retinoids, since all other options for moderate to severe acne contain a topical retinoid."

Pregnancy also changes the choice. The AAD says of tretinoin: "Most experts recommend stopping this treatment during pregnancy," and of azelaic acid: "This is thought to be safe to use during pregnancy." NICE says topical retinoids are "contraindicated during pregnancy and when planning a pregnancy." The pregnancy guide covers azelaic acid in detail.

Scars and marks

For sunken scars, the AAD says "a retinoid or salicylic acid can make scarring less noticeable" when scarring is mild. Skinli's guide to tretinoin for acne scars covers those trials. For flat marks, both help: the AAD says azelaic acid "can also treat the dark spots that appear when acne clears." See adapalene vs tretinoin and azelaic acid for acne for more on each treatment. If you also use niacinamide, the guide to azelaic acid with niacinamide covers that pair.

When to see a doctor

Tretinoin and the 15% and 20% azelaic acid products need a prescription in the U.S., so a doctor is part of the plan from the start. See the prescriber if irritation is strong or does not settle, if acne gets worse after the first weeks, if you notice light or dark patches, or if you become pregnant. Skinli gives general education. A doctor is the right person to diagnose and treat your skin.