Aim was to assess the long-term clinical efficacy of infliximab therapy in patients with Crohn's disease treated in a cohort of 2 tertiary referral centers in the Netherlands. All consecutive patients with Crohn's disease treated with infliximab were assessed. Endpoints were primary clinical efficacy, sustained benefit, efficacy of retreatment, surgical intervention rates, and safety. Sustained benefit was determined by Kaplan-Meier analysis. The estimated 5-year benefit was calculated. A total of 469 patients were included. Median follow-up length was 4.5 years (interquartile range, 2.7-6.8). Seventy patients (15%) had unsuccessful remission induction, and 316 patients received maintenance therapy. Scheduled maintenance regimen was successful in 169 of 276 (61%). Episodic maintenance therapy was successful in 19 of 40 patients (48%). Estimated 5-year sustained benefit was 55.7% (95% confidence interval, 48.8-62.6). Concomitant thiopurines were associated with improved sustained benefit. A second course of infliximab after previous discontinuation was prescribed in 131 patients with similar efficacy rates. Abdominal surgical intervention rate per 100 patient-years was significantly reduced after infliximab initiation in patients with a scheduled maintenance regime (reduction, 2.70; 95% confidence interval, -4.82 to -0.35; P = 0.018). Mortality and malignancy rates were 1.9% (0.39/100 patient-years) and 3.4% (0.70/100 patient-years), respectively. The present study shows an estimated 5-year sustained benefit of 55.7% in patients with Crohn's disease treated with infliximab maintenance therapy. Remission induction and maintenance were equally successful in patients starting infliximab and patients who temporarily stopped and were retreated. Long-term use of infliximab was safe and reduced the need for surgery in patients on scheduled maintenance therapy.