Background: Endoscopic pancreatic sphincterotomy is less widely practiced than biliary sphincterotomy, in part because of the lack of firm data regarding its indications and safety. In addition, recent reports of ductal and parenchymal changes occurring after pancreatic stenting raise concerns about the standard practice of stent placement at the time of pancreatic sphincterotomy. We report our experience with pancreatic sphincterotomy and describe the use of a technique involving overnight nasopancreatic drainage rather than stenting. Methods: We reviewed the records of the 164 pancreatic sphincterotomies performed on 160 patients at our institution between January 1, 1991, and October 1, 1996, comparing procedures done with overnight nasopancreatic catheter placement with those done with stenting or no drainage. We also examined the long-term clinical outcome of patients after pancreatic sphincterotomy. Results: Of the 164 sphincterotomies, 98 were done with overnight nasopancreatic drainage, 50 with stent placement, and 16 with no drainage. Complications (all pancreatitis) were significantly more frequent in the group with no drainage (12.5%) as compared with those with drainage (0.7%); p < 0.003. Nasopancreatic drainage was as safe as stent placement, with no complications after 98 procedures. Pancreatic sphincterotomy was effective when used as primary therapy, with 64% of patients so treated experiencing complete and long-lasting resolution of symptoms after the procedure. Conclusions: Pancreatic sphincterotomy is safe and effective, although pancreatic drainage is required to reduce the incidence of pancreatitis. Overnight nasopancreatic drainage is the method of choice, as it carries as low a complication rate as stent placement, but without the need for a repeat procedure, and presumably without the risk of ductal and parenchymal damage. (Gastrointest Endosc 1998;47:240-9.)