Background/Aims: Evidence for the effectiveness of methotrexate (MTX) in treating inflammatory bowel disease (IBD) is still incomplete. This study assessed the effectiveness, safety and mucosal healing in IBD patients treated with MTX in the Swiss IBD Cohort. Methods: Efficacy was defined by physician assessment or by CD activity index <150 points for Crohn’s disease (CD) or Modified Truelove and Witts activity index <4 points for ulcerative colitis (UC), measured at least after 3 months of MTX therapy. Mucosal healing was evaluated after 3 months or more of therapy. Results: MTX was administered to 341 patients (262 CD; 79 UC) out of 2,660 patients. MTX effectiveness was 59.5% (128/215) in CD and 40.0% (24/60) in UC (chi² = 7.2409, p = 0.007). Among patients on MTX therapy at the time of analysis, remission was obtained in 87.4% (76/87) and 69.2% (9/13) for CD and UC patients respectively. The median duration of MTX therapy was 40 months for CD and 15 months for UC. Occurrence of adverse events was the first reason for treatment discontinuation (39.4% of all cases). The rate of mucosal healing with MTX was 9.5% for CD and 25% for UC patients respectively. Conclusion: MTX therapy was effective for the induction and maintenance therapy in IBD patients, with only a modest mucosal healing ability.