Treatment of acne vulgaris can be challenging for both patients and physicians. Topical retinoids are often considered first-line therapy for the treatment of all but the most severe forms of acne. A variety of formulations of topical retinoids, including adapalene and tazarotene, are available but tazarotene 0.1% gel is widely perceived to be the most efficacious. The goal of this study was to evaluate the efficacy and tolerability of a new, higher concentration of adapalene, adapalene 0.3% gel, compared to tazarotene 0.1% gel in the treatment of acne vulgaris. The primary efficacy outcome was the percent reduction in total lesion count at week 12. Subjects 12 to 35 years of age with acne vulgaris (N=172) participated in a 12-week, randomized, evaluator-blinded, noninferiority study of once-daily therapy with adapalene 0.3% gel or tazarotene 0.1% gel. Subjects in each group achieved clinically significant reductions in total lesion counts at week 12 (61% and 57% median reductions for adapalene and tazarotene, respectively); adapalene 0.3% gel was noninferior to tazarotene 0.1% gel (95% confidence interval [CI]: -5.2-9.6). The adapalene arm was also therapeutically similar to the tazarotene arm in terms of the percent reduction in inflammatory and noninflammatory lesion counts at week 12, as well as in the assessments of acne severity and improvement. Mean tolerability scores for erythema, dryness, scaling, and stinging/burning were consistently lower in the adapalene arm compared to patients treated with tazarotene (P<.014 at week 12, Cochran-Mantel-Haenszel [CMH] test). The worst score for any tolerability parameter in the treatment phase in the adapalene arm was less than 1 (mild). Adapalene was also associated with a lower incidence of treatment-related adverse events when compared to tazarotene (3.5% versus 14%, respectively). Once daily therapy with adapalene 0.3% gel provided similar efficacy (noninferior) to tazarotene 0.1% gel in the treatment of acne vulgaris, but demonstrated a superior tolerability profile.