Recent evidence suggests melasma to be a photoaging disorder. Triple combination creams (TCC; fluocinolone acetonide 0.01%, hydroquinone 4%, and tretinoin 0.05%) remain the gold standard treatment. Picosecond alexandrite laser treatment using a diffractive lens array (DLA) has been identified to be effective for improving photoaging conditions.We aimed to compare the efficacy and tolerance of the picosecond alexandrite laser with those of DLA and TCC in female Asian patients with melasma.Twenty-nine patients were randomly assigned to group A1 (3 laser sessions at 4-week intervals), A2 (5 laser sessions at 4-week intervals), or B (TCC daily for at least 8 weeks and then tapered until the final evaluation). The Melasma Area, Severity Index (MASI) score and VISIA were assessed at baseline, week 12, and week 20. By week 20, the follow-up periods for groups A1 and A2 were 3 months and 1 month, respectively.Nine, 11, and 6 participants in groups A1, A2, and B completed the study, respectively. MASI scores were significantly improved in all 3 groups at weeks 12 and 20. In groups A1, A2, and B, the improvement rates at week 20 were 53%, 38%, and 50%, respectively. VISIA® analysis additionally revealed a significant improvement in spots, porphyria, pores, and brown spots after 3 laser sessions (p<0.05). Group A2 showed greater improvements than group A1 in terms of spots, wrinkles, and pores; however, only red areas were significantly different (p<0.001). All side effects in the 3 groups were transient and gradually subsided after 1 to 3 months.Picosecond alexandrite laser treatment using DLA showed comparable efficacy with TCC for the treatment of melasma. Improvements in texture, spots, wrinkles, and pores were observed in the laser groups. Patients with melasma lesions that exhibit telangiectasia may benefit from additional laser treatment sessions. This article is protected by copyright. All rights reserved.