The safety of endoscopic manometry of the sphincter of Oddi was evaluated in a prospective survey of 158 consecutive procedures in 126 patients with either unexplained pain after cholecystectomy or idiopathic recurrent pancreatitis. The only complication was that of pancreatitis which was defined as the development of abdominal pain in association with a plasma amylase above the reference range. This occurred in 13 patients (8%) and was more frequent (P = 0.001) when the indication for the procedure was idiopathic recurrent pancreatitis (29%) than unexplained pain (6%). Pancreatitis was also more frequent (P = 0.02) in patients with abnormal manometry (14%) than in those with normal manometry (3%) and occurred at highest frequency (50%) in a subgroup of patients with idiopathic recurrent pancreatitis and sphincter stenosis (high sphincter basal pressure). All episodes of pancreatitis were mild with a median increase in hospital stay of 2 days; no patients died. The risk of pancreatitis after endoscopic manometry is relatively low but increases in patients with abnormal sphincter manometry, particularly those with idiopathic recurrent pancreatitis.