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To date, no large-scale studies have evaluated the prognosis of Crohn's disease (CD) over a period of 3 decades in non-Caucasian populations. The aims of this study were to update the current information on the long-term prognosis of CD using a large series of patients and to evaluate changes in treatment paradigms over time and their impact on the prognosis of CD in Korea.We retrospectively analyzed 2043 Korean patients with CD who visited the Asan Medical Center. The study subjects were divided into 3 groups according to the year of diagnosis (cohort 1: 1981–2000, cohort 2: 2001–2005, and cohort 3: 2006–2012).Azathioprine/6-mercaptopurine and anti–tumor necrosis factor agents have been used increasingly more frequently and earlier over the past 30 years, with a 5-year cumulative probability of prescription of 28.9% and 1.4%, respectively, in cohort 1 and 88.1% and 23.7%, respectively, in cohort 3 (P < 0.001). A total of 726 patients (35.5%) underwent intestinal resection, with a cumulative probability of intestinal resection 10, 20, and 30 years after diagnosis of 43.5%, 70.0%, and 76.1%, respectively. The cumulative probability of surgery was significantly lower in cohort 3 than in cohort 1 (P = 0.012). Early use of azathioprine/6-mercaptopurine was significantly associated with delayed need for intestinal resection by multivariate Cox analysis (hazard ratio: 0.63, 95% confidence interval: 0.46–0.85).Korean patients with CD may have a similar clinical course to Westerners, as indicated by the intestinal resection rate. The surgery rate has decreased over time, and early use of azathioprine/6-mercaptopurine was related to its decrease.