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Acute pancreatitis has occasionally been associated with Crohn's disease (CD), but whether a causal association exists remains unclear. We sought to determine the frequency of etiologies in a consecutive series of patients with CD with acute pancreatitis. Methods: A centralized diagnostic index was used to identify all patients with CD with acute pancreatitis that were evaluated at Mayo Clinic Rochester between 1976 and 2001. Both diagnoses were made or confirmed at our institution. Records were abstracted for demographics, presenting symptoms, diagnostic tests, risk factors of pancreatitis, treatment, and follow-up. Results: Forty-eight patients with CD with pancreatitis were identified. The median age at diagnosis of acute pancreatitis was 47 years (range, 31-91 yr). Forty-six (96%) met biochemical criteria for acute pancreatitis. The most sensitive radiographic tests were abdominal computed tomography (70%) and abdominal ultrasound (46%). The etiology of pancreatitis was considered to be gallstones (21%), significant alcohol intake (15%), use of purine analogs (13%), duodenal Crohn's involvement (12%), postendoscopic retrograde cholangiopancreatography complications (10%), postoperative complications (12%), use of other medications (4%) and idiopathic (8%). The median length of hospitalization was 7 days (range, 0-40 d). Ten patients (21%) had recurrence of acute pancreatitis. Three patients (6%) were subsequently diagnosed with pancreatic cancer. Conclusions: A definite etiology could be identified in most patients with CD with acute pancreatitis. Gallstones and alcohol accounted for more than one third of cases, whereas CD, either because of duodenal involvement or medications used for its treatment, accounted for more than one quarter of the cases. A small proportion of patients remained idiopathic.