Background: Pancreatic resection is associated with a high incidence of postoperative complications, some of which require reoperation. Aims: To analyze the incidence of and risk factors for reoperation following pancreatectomy. Methods: Pre- and postoperative information and procedure characteristics of 15,549 patients having undergone pancreatectomy in 435 hospitals participating in the American College of Surgeons National Surgical Quality Improvement Program from 2011 to 2014 were analyzed. Results: A total of 773 (5.0%) patients required reoperation within 30 days of their index pancreatectomy. Patients requiring reoperation were more likely to be younger (mean ± standard deviation, 62.6 ± 13.2 vs. 64.1 ± 12.2 years, p < 0.001), male (60 vs. 49%, p < 0.001), to have respiratory comorbidities, lower preoperative serum albumin (3.7 ± 0.68 vs. 3.8 ± 0.62 mg/dl, p < 0.001), higher total bilirubin (1.7 ± 2.7 vs. 1.5 ± 2.4 mg/dl, p = 0.02), and higher American Society of Anesthesiologists (ASA) class than those who did not undergo reoperation. Other factors associated with increased incidence of reoperation included longer mean operative duration at the index procedure, postoperative transfusion requirement, wound complications, and cardiorespiratory, renal, thromboembolic, and infectious events. Multivariate regression analysis identified male sex, preoperative serum albumin <3.5 mg/dl, ASA class of 3 or 4, pancreaticoduodenectomy, and total pancreatectomy as the strongest predictors for reoperation after index pancreatic resection. Complication and readmission rates were significantly higher for those undergoing reoperation. Conclusion: Patient characteristics and procedural factors contribute to reoperation after pancreatectomy in this largest and most diverse sample to date. Further investigation to identify perioperative strategies for mitigating this risk is required to improve the safety of pancreatic resection. © 2017, Springer Science+Business Media New York.