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Background: There are paucity of data regarding the utility of methotrexate (MTX) in the management of ulcerative colitis (UC). The aim of this study was to describe the efficacy of MTX in achieving steroid-free remission., Methods: A retrospective cohort study was conducted using the nationwide Veterans Affairs database to identify steroid-dependent patients with UC using MTX for the period 2001 to 2011. Patients were followed up for 15 months after MTX initiation by tracking their prednisone, MTX, thiopurines, and infliximab dispense. Endpoints were: (1) successful remission, defined as cessation of prednisone filling activity while continuing MTX; (2) failure with continuance, failure to be weaned off steroids while continuing MTX; (3) failure with discontinuance, cessation of MTX while continuing steroids., Results: We included 91 patients with UC with mean age 59 years. The average weekly dose for oral and parenteral MTX was 14 and 25 mg/week, respectively. The average daily dose for prednisone within the oral MTX and parenteral MTX groups was 12 and 25 mg/day, respectively. By the 12th month of follow-up, 37% and 30% of patients on oral and parenteral MTX, respectively, were able to discontinue steroid. There was a nonsignificant trend toward dose reduction of steroids in those who were concomitantly taking oral MTX and steroids., Conclusions: Our study represents the largest cohort of patients with MTX and UC reported to date and suggests that approximately one-third of patients were successfully weaned off steroids with MTX therapy. MTX should be considered in the long-term management of patients with UC on steroids.