The long-term benefits of combining scheduled infliximab with concomitant immunomodulators [azathioprine or 6-mercaptopurine (6-MP)] in patients with Crohn's disease are unclear. Historical cohort followed for 5 years after initiation of infliximab for active Crohn's disease. Data were available on 123 patients who received scheduled maintenance infliximab infusions, for up to 5 years after initiation of infliximab. Clinical remission rates in the entire cohort were 73% (82/113) at 1 year, 65% (65/100) at 2 years, and 58% (21/36) at 5 years. Remission rates with maintenance infliximab were significantly improved in those receiving concomitant immunomodulators at 1 year (86% versus 68%, P = 0.03), but not at 2 years (80% versus 72%, P = 0.4). In a multivariate logistic regression model, concomitant immunomodulator use was not associated with a significantly improved odds ratio of remission in patients on maintenance infliximab [odds ratio (OR) 1.1, 95% confidence intervals (CI) 0.9-1.2, P = 0.9]. The risk of surgery was significantly reduced in those receiving immunomodulators at the commencement of maintenance infliximab (OR 0.3, 95% CI 0.1-0.7, P = 0.01), but not in patients who continued maintenance concomitant therapy (OR 0.4, 95% CI 0.1-1.5, P = 0.1). The combination of maintenance infliximab and an immunomodulator produced modest improvements in outcomes beyond maintenance infliximab alone in this cohort.