Purpose: To calibrate real-world evidence (RWE) against randomized controlled trials (RCTs) in ulcerative colitis (UC) by replicating the SUCCESS trial on the effectiveness of infliximab in patients with UC, using U.S. and French healthcare claims data. Methods: The SUCCESS trial showed improved remission with infliximab and thiopurines combined compared to infliximab monotherapy in patients with UC. Based on two U.S. commercial insurance databases (IBM MarketScan and Optum) and the French nationwide health insurance database (SNDS) from 2004 through 2019, all patients with UC who initiated combination therapy or infliximab alone were identified. The primary outcome was a composite endpoint of treatment failure - hospitalization relatedto UC or colectomy, treatment switch to another biologic or immunosuppressant, or use of corticosteroids 16 weeks after infliximab initiation. We estimated risk ratios (RRs) with 95% confidence intervals (CIs) after 1:1 propensity score (PS) matching. Results: Among 620 PS-matched pairs of combination therapy and infliximab monotherapy users, treatment failure occurred in 124 (20.0%) and 170 (27.4%) patients initiating combination therapy and infliximab monotherapy, respectively. Like in SUCCESS, the risk of treatment failure was decreased with combination therapy in the overall cohort (RR=0.73; 95%CI: 0.60–0.90). Findings were consistent across MarketScan, Optum, and SNDS: RR=0.76 (0.52–1.02), 0.82 (0.54–1.24), and 0.61 (0.41–0.90), respectively. Similar results were observed for each individual component of the composite endpoint. Conclusions: RWE results across three large databases were consistent with RCT findings. These findings provide support for the use of RWE to assess treatment effectiveness in UC.