Topical treatments, such as adapalene and benzoyl peroxide (BPO), are popular in mild-to-moderate acne vulgaris. This study aimed to compare the efficacy, safety and tolerability of adapalene and BPO in mild acne vulgaris. In this single-center, randomized, double-blind, clinical trial, 60 patients with mild acne vulgaris received either topical adapalene 0.1% gel or topical BPO 2.5% gel on their face once daily for two months. The changes of acne lesion count (efficacy), any adverse effect (safety), and the patients' overall satisfaction (tolerability) were compared after 3 months of follow-up. In both groups the mean number of noninflammatory, inflammatory and total lesions decreased significantly from baseline (10.77±5.54, 9.73±5.09, and 20.50±7.54, respectively in adapalene group; 11.50±5.92, 8.43±5.45, and 19.93±9.01, respectively in BPO group) to the third month (1.70±1.68, 0.33±0.66, and 0.50±0.78, respectively in adapalene group; 4.23±4.14, 0.33±0.71, and 4.13±4.44, respectively in BPO group; P<0.001 for all), posttreatment. Although the mean number of inflammatory lesions was significantly lower in BPO receivers only at first month (P=0.001), the mean number of noninflammatory and total lesions was significantly lower in adapalene group at second (P= 0.04 and 0.03, respectively) and third (P=0.02 and <0.001, respectively) months, posttreatment. The adverse events were minimal and self-limited (26.7% in adapalene group, 20% in BPO group, P=0.54). The patients' overall satisfaction was good-excellent in 93.3% of adapalene receivers vs. 73.3% in BPO group (P=0.08). Both topical adapalene 0.1% and BPO 2.5% gels seem safe and effective in mild acne vulgaris, with a marginal tendency toward the former.