Hyperamylasemia and acute pancreatitis represent the most frequent major complication after endoscopic retrograde cholangiopancreatography (ERCP), developing in 1-30% of cases. To determine the incidence of hyperamylasemia and acute pancreatitis after ERCP, and to assess the utility of rectal indomethacin to prevent these events. A randomized clinical trial. During a 12-month period 150 patients were included. They were divided up into a study group (n = 75), where 100 mg of rectal indomethacin were administered 2 hours prior to the procedure, and a control group (n = 75), which received rectal glycerin. Two hours after ERCP serum amylase levels were measured and classified as follows: 0or=600 IU/L. Clinical pancreatitis episodes were quantified and classified according to Ranson's criteria. Gender distribution: 100 women and 50 men. Mean age: 55.37 +/- 18.0 for the study group, and 51.1 +/- 17.0 for the control group. A diagnosis of benign pathology was present in 56 (74.7%) cases in the study group, and 59 (78.7%) controls. After ERCP 13 (17.3%) patients in the study group and 28 (37.3%) in the control group developed hyperamylasemia (p (2) 0.05). Hyperamylasemia > 600 IU/L was found in 3 patients in the study group, and in 10 in the control group (p = 0.001). Mild pancreatitis was detected in 4 (5.3%) patients in the study group, and in 12 (16%) patients in the control group (p = 0.034). There were no deaths or adverse drug reactions. Rectal indomethacin before ERCP decreases the risk of hyperamylasemia and pancreatitis. Indomethacine is a feasible, low-cost drug with minimal or nil side effects.