Long‐Term Comparative Effectiveness and Safety of Oral Versus Topical Tranexamic Acid for Melasma: A 24‐Month Single‐Center Retrospective Cohort Study (2020–2024)

Background Long‐term comparative data for oral versus topical tranexamic acid (TXA) in melasma are limited. Objective To compare 24‐month effectiveness, relapse, and safety of oral vs. topical TXA. Methods In this single‐center retrospective cohort (2020–2024), 244 Asian women with melasma initiated oral TXA ( n = 122) or topical TXA ( n = 122). The primary endpoint was change in Melasma Area and Severity Index (MASI) from baseline to 24 months (ΔMASI). Repeated MASI measurements (3–24 months) were analyzed using an adjusted linear mixed‐effects model incorporating prespecified baseline covariates; relapse was analyzed with Cox regression, and adverse events (AEs) were recorded. Results Baseline MASI was similar between groups (18.2 ± 7.4 vs. 17.5 ± 7.9). At 24 months, observed MASI was 8.8 ± 5.5 ( n = 48) with oral TXA and 9.6 ± 5.6 ( n = 51) with topical TXA. Oral TXA was associated with greater MASI reduction at 24 months (oral–topical ΔMASI, −1.54; 95% CI, −2.33 to −0.75; p < 0.001). Relapse rates were comparable (29.5% vs. 25.4%; HR: 1.20; 95% CI: 0.74–1.95). Any AE was more common with oral TXA (41.0% vs. 22.1%); serious AEs were rare (one severe gastrointestinal event with oral TXA and two severe local reactions with topical TXA), and no thromboembolic events were recorded. Conclusion Over 24 months, oral TXA achieved larger MASI improvements than topical TXA but had higher AE rates; relapse was similar.