Benzoyl peroxide and adapalene are among the most effective topical agents used in the treatment of acne. We planned an open-labeled, prospective study to compare the effects and side effects of these two drugs alone and in combination in the treatment of acne vulgaris. One hundred and five consecutive patients (30 men and 75 women) with acne vulgaris were included in this study. The patients were randomly divided into three groups with 35 patients in each. The groups were randomly assigned to 0.1% adapalene gel, 5% benzoyl peroxide lotion, or combination of 0.1% adapalene gel +5% benzoyl peroxide treatment. Acne lesions were classified as noninflammatory (open and closed comedones) and inflammatory (papule, pustule, nodule, cyst), and the lesions on the face were counted before the therapy, during the control visits, and after the treatment. Erythema, dryness, burning, and other side effects were recorded during the treatment. The mean age of the patients was 18.44 +/- 3.75 years. Eight patients were excluded because of noncompliance with the treatment regimen or the follow-up schedule, and four patients were excluded due to allergic contact dermatitis. The study revealed that all three therapy protocols were effective in treating noninflammatory and inflammatory lesions in acne vulgaris (p<0.05) and that there was no significant difference between the groups in efficacy or side effects (p>0.05). Adapalene and benzoyl peroxide are effective and well tolerated agents for acne vulgaris; combination therapy has no superiority over adapalene or benzoyl peroxide alone.