BACKGROUND AND AIMS: Etrasimod is an oral, once-daily, selective sphingosine 1-phosphate (S1P)(1,4,5) receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC). In this post hoc analysis, induction and maintenance efficacy of etrasimod 2 mg vs placebo were assessed by baseline Mayo endoscopic subscore (ES) in ELEVATE UC 52 and ELEVATE UC 12. METHODS: Moderate and severe endoscopic disease were defined as a centrally-read ES of 2 and 3, respectively. Efficacy endpoints were evaluated at Weeks 12 (pooled population) and 52 (ELEVATE UC 52). Subgroup analyses were stratified by baseline modified Mayo score (4-6 vs 7-9) and prior biologic/Janus kinase inhibitor exposure. RESULTS: Overall, 235 patients with moderate and 292 with severe endoscopic disease received etrasimod; 112 and 148 patients, respectively, received placebo. At both time points, significantly greater proportions of patients receiving etrasimod compared with placebo achieved clinical remission in the moderate (Week 12: 38.3% vs 17.9%; Week 52: 36.5% vs 14.3%; both P < .001) and severe (Week 12: 18.2% vs 6.1%; Week 52: 29.4% vs 3.4%; both P < .001) endoscopic disease subgroups. Similar efficacy was observed at Weeks 12 and 52 for most endpoints. The proportion of etrasimod-treated patients with severe endoscopic disease achieving endpoints was generally numerically higher at Week 52 vs Week 12, relative to placebo. Subgroup analysis findings were generally similar. CONCLUSIONS: Etrasimod demonstrated significant induction and maintenance efficacy over placebo in both moderate and severe endoscopic disease. Response to etrasimod in patients with severe endoscopic disease may continue to improve beyond 12-week induction therapy (ClinicalTrials.gov: NCT03945188; NCT03996369).