Background:Melasma, a common disorder of hyperpigmentation, is often difficult to treat. Although 10% zinc sulfate solution has been reported to be useful for patients with melasma, controlled trials are lacking.Materials and Methods:72 women with moderate to severe melasma were divided randomly into 2 groups. Group A were treated with 10% zinc sulfate solution and group B with 4% hydroquinone cream twice-daily. The results were evaluated by photoevaluation by patients based on subjective satisfaction and a blinded dermatologist using MASI score. Assessments were obtained at baseline and at 2 and 6 months after starting treatment.Results:According to MASI score changes during treatment, there was a reduction in both groups at 2 months, however, the reduction in group B was more significant (the reduction in mean ± SD MASI was 0.7 ± 0.7 in group A vs. 2.7 ± 1.6 in group B). In addition, the patients in group B continued to decrease MASI score for the remainder of the study period at 6 months follow-up (0.3 ± 0.5) in comparison with patients in group A who did not show more reduction in MASI score.Conclusions:The study indicates that topical zinc sulfate is not as effective in treating disease as was observed in the previous open study. A comparative study with sunscreen and placebo is necessary to determine if topical zinc sulfate is truly superior to sunscreen and placebo in this respect.