Acne vulgaris is a common dermatologic disease that most frequently affects adolescents and young adults. Over-the-counter (OTC) acne treatment regimens are increasingly being used by individuals with acne. To compare the efficacy, user satisfaction, and tolerability of the OTC regimens MaxClarity™, Proactiv®, and Murad® in the treatment of mild and moderate acne. Two randomized, evaluator-blinded, split-face studies were conducted, each involving 20 subjects with acne, to evaluate MaxClarity against Proactiv (study 401) and MaxClarity against Murad (study 404) over 8 weeks. Clinically and statistically significant reductions in acne lesion counts were achieved at 8 weeks compared with baseline for each regimen using MaxClarity, Proactiv, and Murad. Similar reductions in lesion counts and improvements in Investigator's Static Global Assessment grades were observed between MaxClarity and either Proactiv or Murad, in the respective studies. MaxClarity was well tolerated, with no treatment-related adverse events observed in any treatment group and no discontinuations due to adverse events. Overall, most subjects were satisfied with all study treatments. MaxClarity is an effective alternative to either Proactiv or Murad for use in the treatment of mild and moderate acne.