Background Melasma is an acquired hypermelanosis predominantly affecting the face of women. It is often recalcitrant to treatment with hypopigmenting agents. Objective To assess the efficacy of a nonhydroquinone cream (Amelan M®) vs. another (Mela-D®) as treatment for melasma. Methods Twenty-two French women with bilateral epidermal and/or mixed melasma were enrolled in a split-faced prospective trial lasting 4 months during summer season weeks. Twelve patients applied once-daily Amelan M® to one side of the face with sun-protective factor 60 UVA sunscreen each morning and Mela-D® once-daily to the other side of the face. Pigmentation was measured objectively using a mexameter and the melasma area and severity index (MASI) were measured subjectively. Results The mean decrease of pigmentation was statistically significant on the MASI with both cream and only with Amelan M with the mexameter. Some adverse side effects were observed. Conclusions Amelan M® is really more effective than Mela D® cream on melasma. Even though some side effects were observed patients preferred the Amelan M-treated side