Résumé : BACKGROUND AND STUDY AIMS: Endoscopic pancreatic sphincterotomy is indispensable for many therapeutic endoscopic maneuvers, but is also associated with a higher risk of pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP). In this study, this subgroup of patients was investigated in order to identify risk factors and protective factors. PATIENTS AND METHODS: A retrospective chart review identified 572 endoscopic pancreatic sphincterotomies that met the inclusion criteria. Charts were examined for indications, endoscopic technique, and outcomes, including pancreatitis. RESULTS: A total of 477 patients underwent 572 endoscopic pancreatic sphincterotomies during a 5-year period. Indications for sphincterotomy included chronic pancreatitis (n = 398), access for tissue sampling (n = 52), acute recurrent pancreatitis (n = 45), transpapillary drainage of a pancreatic pseudocyst (n = 32), precut access to the common bile duct (n = 29), and others (n = 16). Pancreatic duct drainage was performed in 69.1 % of the procedures (nasopancreatic catheter, n = 290, or pancreatic stent placement, n = 105). Post-ERCP pancreatitis occurred in 69 cases (12.1 %) and was severe in 10. The multivariate analysis identified female sex as being associated with a higher risk of pancreatitis, while an elevated C-reactive protein level, pancreatic ductal stones, sphincterotomy at only the major papilla, and pancreatic duct drainage with a nasopancreatic catheter or stent were associated with a lower risk. CONCLUSIONS: This large series of patients undergoing endoscopic pancreatic sphincterotomy provides further evidence that both patient characteristics and technical factors modify the risk profile for post-ERCP pancreatitis. In addition to providing further definition of which patients are at risk, it also suggests that pancreatic duct drainage is an independently significant protective maneuver.