Background: Earlier introduction of immunomodulators (IM) thiopurine or methotrexate is advocated to improve Crohn's disease (CD) outcomes, but whether abdominal surgery can be prevented remains controversial. Methods: A specialist-referred cohort of CD was recruited from 1970 to 2009. Early IM use was defined as commencement of azathioprine or methotrexate within 3 years of CD diagnosis and adherence of at least 6 months. Propensity score matching was conducted to correct for confounders influencing early IM introduction. Outcomes of interest were rates of initial and recurrent major abdominal surgery for CD and their predictive factors. Results: A total of 1035 consecutive patients with CD (13, 061 patient-years) were recruited. The risk of first and recurrent major abdominal surgery at 1, 5, and 10 years were 17.5%, 28.4%, and 39.5% and 5.9%, 19.0%, and 33.3%, respectively. Early IM use increased over time from 1.3% to 55.3% (P < 0.0001) and was a significant independent predictor of lower rates of initial abdominal surgery (hazard ratio [HR], 0.45; 95% confidence interval [CI]< 0.35-0.69), recurrent abdominal surgery (HR, 0.44; 95% CI, 0.25-0.79) and perianal surgery (HR, 0.30; 95% CI, 0.16-0.56). Using propensity score matching, early IM significantly reduced surgical rates (HR, 0.54; 95% CI, 0.37-0.79). Number needed to treat to prevent a surgical event at 5 years from diagnosis and after initial surgery was 6.99 (95% CI, 5.34-11.95) and 8.59 (95% CI, 6.26-23.93), respectively. Conclusions: Early IM use with thiopurines or methotrexate was significantly associated with the reduced need for abdominal and perianal surgery in CD.