This comparative study’s main objective was to assess topical 5% cysteamine’s efficacy and safety versus 4% hydroquinone in women’s facial melasma treatment. Topical 5% cysteamine is an antioxidant and tyrosinase inhibitor that is effective in the treatment of melasma. However, no study has compared the performance of topical cysteamine to hydroquinone for facial melasma to date. A quasi‐randomized, multicenter, evaluator‐blinded clinical trial was conducted on 40 women with facial melasma who were submitted to the nightly application of 5% cysteamine (CYS) or 4% hydroquinone (HQ) on hyperpigmented areas for 120 days. Both groups were required to use tinted sunscreen (SPF 50; PPD 19). Subjects were assessed at the inclusion and after 60 and 120 days of treatment for mMASI, MELASQoL, and the difference in colorimetric luminosity between melasma and the adjacent unaffected skin. The Global Aesthetic Improvement Scale was used to assess the difference in skin appearance through standardized photographs.

The average reduction of the mMASI scores were 24% for CYS and 41% for HQ at 60 days, 38% for CYS, and 53% for HQ at 120 days. The photographic evaluation revealed up to 74% improvement for both groups, without statistically significant differences. Cysteamine proved to be safe, well‐tolerated, and effective, despite its inferior performance to hydroquinone in decreasing mMASI and MELASQoL in melasma treatment.