Background and Aims Thiopurines are commonly used for treating ulcerative colitis (UC), despite the fact that controlled evidence supporting their efficacy is limited. The aim of this study was to evaluate the long-term outcome of thiopurines as maintenance therapy in a large cohort of UC patients. Methods All UC patients receiving thiopurine monotherapy at three tertiary IBD centers from 1995 to 2015 were identified. The primary endpoint was steroid-free clinical remission. Secondary endpoints were mucosal healing (MH), defined as Mayo endoscopic subscore 0, long-term safety, and predictors of sustained clinical remission. Results We identified 192 patients, contributing a total of 747 person-years of follow-up (median follow-up 36 months, range 1–210 months). Steroid dependency was the most common indication for thiopurine treatment (58%). Steroid-free remission occurred in 45.3% of patients; 36.3% stopped thiopurines because of treatment failure and 18.2% for adverse events or intolerance. The cumulative probability of maintaining steroid-free remission while on thiopurine treatment was 87%, 76%, 67.6%, and 53.4% at 12, 24, 36, and 60 months, respectively. MH occurred in 57.9% of patients after a median of 18 months (range 5–96). No independent predictors of sustained clinical remission could be identified. Conclusions Thiopurines represent an effective and safe long-term maintenance therapy for UC patients.