Melasma is an acquired hypermelanosis predominantly affecting the face of women. It is often recalcitrant to treatment with hypopigmenting agents. To assess the efficacy of a nonhydroquinone cream (Amelan M) vs. another (Mela-D) as treatment for melasma. 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. 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. 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.