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Melasma is a common pigmentary disorder that is often difficult to treat. Tranexamic acid (TA) has emerged as a promising treatment for melasma; however, few controlled studies exist.To determine the efficacy of oral TA in patients with moderate-to-severe melasma.Patients with moderate-to-severe melasma were treated with 250 mg of TA or placebo capsules twice daily for 3 months and sunscreen followed by 3 months of treatment with sunscreen only. The primary outcome measure was the modified Melasma Area and Severity Index (mMASI) score.A total of 44 patients were enrolled and 39 completed the study. At 3 months, there was a 49% reduction in mMASI score in the TA group versus 18% in the control group. Patients with severe melasma improved more than those with moderate melasma. Three months after treatment was stopped, there was a 26% reduction in mMASI score in the TA group compared with the baseline visit versus a 19% reduction in the placebo arm. No serious adverse events were noted in either group.Single-center study enrolling predominantly Hispanic women.Oral TA appears to be an effective treatment for moderate-to-severe melasma with minimal side effects.