Background: Pancreatitis is the most frequent complication of ERCP. Injury to the papilla during ERCP could obstruct pancreatic duct outflow and initiate pancreatitis. A randomized prospective study was performed to evaluate the effect of pancreatic duct stent placement on the frequency and severity of post-ERCP pancreatitis in a selected group of patients. Methods: The study group consisted of patients over 18 years of age at high risk for post-ERCP pancreatitis because of a difficult cannulation, sphincter of Oddi manometry, and/or the performance of endoscopic sphincterotomy. Patients were prospectively randomized to have a pancreatic duct stent placed or no stent upon completion of the ERCP. The endoprosthesis used was either a 5F nasopancreatic catheter or 5F, 2-cm long pancreatic stent. Study endpoints were the frequency and severity of post-ERCP pancreatitis. Results: Patients undergoing pancreatic duct stent placement had a lower frequency of post-ERCP pancreatitis as compared with those in the control group (28% vs. 5%; p < 0.05). Pancreatitis tended to be less severe in patients who had pancreatic duct drainage. Conclusions: Pancreatic duct stent insertion after ERCP reduces the frequency of post-ERCP pancreatitis in patients at high risk for this complication. (Gastrointest Endosc 2003;57:291-4.)