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The aim of the study was to assess whether azathioprine and antitumour necrosis factor (TNF) treatment decrease the long-term need for surgery in patients with Crohn's disease.This was an observational study of a referral centre cohort. The cumulative incidence of the first Crohn's disease-related major abdominal surgery was estimated using the Kaplan-Meier method, and independent predictors of surgery were identified using Cox proportional hazards regression with propensity scores adjustment. Receiver operating characteristic (ROC) analysis was used to identify optimal cut-offs for duration of maintenance treatments. The electronic charts of 296 incident cases of Crohn's disease from Nancy University Hospital, France, diagnosed between 2000 and 2008, were reviewed through January 2010.The median follow-up time per patient was 57 months. Seventy-six patients (26%) underwent at least one major abdominal surgical procedure. The cumulative probabilities of the first Crohn's disease-related major abdominal surgery were 6.5, 25.9 and 44.3 at 1, 5 and 9 years, respectively. In the ROC analysis, the duration of anti-TNF and azathioprine treatment had significant cut-off values (≤ 475 days ~16 months and ≤ 45 days ~1.5 months, respectively) with positive likelihood ratios (PLRs) of 1.52 (p0.0001) and 1.51 (p = 0.003) for the first Crohn's disease-related major abdominal surgery. Using multivariate Cox proportional hazards regression analysis (after propensity score adjustment), independent positive predictors of major abdominal surgery were stricturing (HR = 12.01; 95% CI 5.97 to 24.17) or penetrating (HR = 10.77; 95% CI 4.87 to 23.80) disease behaviour at diagnosis, duration of anti-TNF treatment of16 months (HR = 3.86; 95% CI 1.77 to 8.45) and duration of azathioprine treatment of1.5 months (HR = 2.00; 95% CI 1.20 to 3.34).Non-complicated inflammatory disease behaviour and long-term anti-TNF treatment are associated with a lower risk for surgery whereas azathioprine only modestly lowers this risk.