Background & Aims: The natural history of pediatric Crohn's disease and risk factors necessitating surgery have not been thoroughly described. Methods: In a geographically derived incidence cohort diagnosed from 1988 to 2002, we identified 404 Crohn's disease patients (ages, 0–17 years at diagnosis) with a follow-up time ≥2 years. Results: Median follow-up time was 84 months (range, 52–124 months). The most frequent disease location at diagnosis was the terminal ileum/colon (63%). Follow-up was characterized by disease extension in 31% of children. Complicated behavior was observed in 29% of children at diagnosis and 59% at follow-up. Kaplan–Meier survival estimates of the cumulative incidence of surgery were 20% at 3 years and 34% at 5 years from diagnosis. Multivariate Cox models showed that both structuring behavior at diagnosis (hazard ratio HR, 2.54; 95% confidence interval CI: 1.58–4.01) and treatment with corticosteroids (HR, 2.98; 95% CI: 1.64–5.41) were associated with increased risk for surgery, whereas treatment with azathioprine (HR, 0.51; 95% CI: 0.33–0.78) was associated with decreased risk. Azathioprine was introduced earlier in the course of disease in patients not undergoing surgery than in patients requiring surgery. Conclusions: Pediatric Crohn's disease was characterized by frequent occurrence, with time, of a severe phenotype with extensive, complicated disease. Immunosuppressive therapy may improve the natural history of this disease and decrease the need for performing surgery.