The aim of the present prospective study was to investigate whether endoscopic sphincterotomy may be useful in preventing recurrence of acute pancreatitis in patients with gallstones and a high anesthesiological risk of cholecystectomy. Twenty-six elderly patients with severe cardiopulmonary, hepatic, and renal diseases were considered. Endoscopic sphincterotomy was successful in 19 cases (group A: mean age, 78.4 years; range, 71-87) and failed in 7 patients (group B: mean age, 79.8 years; range 73-85). In the follow-up period biliary pain without an increase in pancreatic serum enzymes occurred in six patients in group A and in all patients in group B (p = 0.002); recurrence of acute biliary pancreatitis with a need for hospitalization occurred in one patient in group A and in four patients in group B (p = 0.01). These results suggest that endoscopic sphincterotomy may be considered a very useful option in reducing the recurrence of acute biliary pancreatitis in elderly patients with gallstones and a high anesthesiological risk of cholecystectomy.