A randomized, multicenter, investigator-blinded, active- and vehicle-controlled study was conducted to evaluate the efficacy and safety of adapalene gel 0.3% versus adapalene gel 0.1% and the corresponding gel vehicle. Subjects were assigned randomly to receive either adapalene gel 0.3%, adapalene gel 0.1%, or vehicle once daily for 12 weeks. A total of 214 subjects with moderate to moderately severe acne vulgaris were enrolled, and 85% of subjects completed the study. Adapalene gel 0.3% was significantly superior to adapalene gel 0.1% in total and noninflammatory lesion counts and in global severity score (P < .05 for all). A concentration-dependent increase in clinical benefit for all efficacy assessments was observed. As expected, there were also statistically significant differences in all efficacy parameters in the adapalene gel 0.3% group relative to the vehicle group (P < .001 for all). Treatment-related adverse events were mostly mild-to-moderate and similar between active groups. The results of this study show that adapalene gel 0.3% was superior to adapalene gel 0.1% and vehicle in the treatment of moderate to moderately severe acne while retaining a similar safety and tolerability profile to adapalene 0.1% gel.