Melasma is a common hyperpigmentation of the face or neck that can have severe adverse psychological and emotional effects on affected individuals. Although a variety of treatments have been used over the years, results have typically been less than satisfactory. An open-label, community-based trial was undertaken at 393 centers in the United States, enrolling 1290 patients representing a broad range of races/ethnicities and all Fitzpatrick skin types, to evaluate the efficacy and safety of a new melasma treatment that combines fluocinolone acetonide 0.01%, hydroquinone 4.0%, and tretinoin 0.05% (FA+HQ+RA) in a hydrophilic cream formulation. An additional objective of the study was to assess the impact of this therapy on the quality of life. Efficacy and safety were evaluated at 4 and 8 weeks, and changes in a variety of quality of life parameters were analyzed at the conclusion of the study. All measures of efficacy showed that FA+HQ+RA significantly (p<0.0001) improved melasma at 4 weeks with further improvement at 8 weeks across all races/ethnicities and Fitzpatrick skin types. The treatment was safe and well tolerated. After 8 weeks of therapy, patients reported that FA+HQ+RA had provided a variety of benefits that had enhanced their quality of life.