Background & Aims Acute pancreatitis (AP) is often the initial presentation of pancreatic cancer (pancreatic adenocarcinoma PaCa). We evaluated the risk of PaCa after AP. Methods We performed a retrospective study of patients with AP who sought care in the Veterans Health Administration from 1998 through 2007. We excluded patients with pre-existing PaCa or recurrent AP and those who had the first episode of acute pancreatitis, from 1998 through 2000. Results Of 495,504 patients with Veterans Health Administration inpatient and outpatient records, 5720 were diagnosed with AP (1.15%) and 710 were diagnosed with PaCa (0.14%), from 2000 through 2007. Seventy-six patients had AP within 2 years before being diagnosed with PaCa (10.7% of all patients with cancer diagnosed during that period). The risk for PaCa was greatest in the first year after AP (14.5 per 1000 patient-years) and then decreased rapidly. Risk for PaCa was negligible in patients <40 years old. The incidence of PaCa within the first year after AP was 7.69 per 1000 patient-years in fifth decade of life and reached 28.67 after the seventh decade. Time to diagnosis of PaCa after AP was ≤2 months for 34 patients, 3–12 months for 35 patients, 13–24 months for 7 patients, and >24 months for 10 patients. Conclusions A significant number of patients with PaCa initially present with AP; the diagnosis of cancer is often delayed by up to 2 years. We suggest that PaCa be routinely considered as a potential etiology of AP in patients ≥40 years old.