Melasma is a common pigmentary disorder among Asians and treatment is challenging. Oral tranexamic acid (TA) has emerged as a potential treatment for refractory melasma. Large-scale studies on its use, outcomes, and safety are limited. We sought to evaluate treatment outcomes and adverse effects of oral TA in melasma in an Asian population. We conducted a retrospective analysis of patients who received oral TA for melasma in a tertiary dermatologic center from January 2010 to June 2014. In all, 561 patients (91.4% female, 8.6% male) were enrolled. Median duration of treatment was 4months. Themajority (503 [89.7%]) improved, 56 (10.0%) had no improvement, and 2 (0.4%) worsened. Patients without family history of melasma had better response rates than those with family history (90.6% vs 60.0%, P=.01). Of the 503 who improved, response was seen within 2months of TA initiation, with a relapse rate of 27.2%. Adverse events occurred in 40 (7.1%). Most were transient, but 1 developed deep vein thrombosis requiring prompt discontinuation. She was later given the diagnosis of familial protein S deficiency. This was a retrospective study. Oral TA may be an effective adjunct for refractory melasma. Careful screening for personal and familial risk factors for thromboembolism should be done before initiation.