We are reporting on an evaluator-blinded, multicenter, open-label clinical study to compare the efficacy and safety of sodium L-ascorbyl-2-phosphate (APS) 5% lotion with that of adapalene (ADP) 0.1% gel for facial acne treatment. Sixty patients were randomized to apply either APS or ADP for 12 weeks. Among 53 patients who completed the study, APS treatment was consistently superior to ADP treatment in inflammatory acne lesion reduction at any study period. The overall study results show the superior efficacy and safety of APS 5% lotion compared with that of ADP 0.1% gel in the treatment of acne vulgaris. APS is a vitamin C derivative and is very effective in removing active oxygen species. Oxidation of squalene or fatty acid is thought to induce comedogenesis and is, therefore, pathogenic of acne. The efficacy of APS in acne treatment may be attributed to its oxidation inhibitory action on squalene and fatty acid by removing the active oxygen species.