Abstract OBJECTIVE: The aim of this prospective controlled study was to determine whether prophylactic corticosteroids decrease the incidence of post-ERCP pancreatitis. METHODS: A double-blind comparison of hydrocortisone (100 mg by i.v. infusion immediately before endoscopy) with placebo (sodium chloride administered in the same fashion). A total of 535 patients (286 women and 249 men, with an average age of 58.6 yr) who were scheduled to undergo diagnostic or operative ERCP underwent randomization. Six patients were excluded from the final evaluation for various reasons. The remaining 529 patients, 263 in the hydrocortisone group and 266 in the placebo group, were analyzed. Patients were divided into subgroups with regard to high risk factors for acute pancreatitis after ERCP. RESULTS: The overall incidence of acute pancreatitis was 5.3% (28 of 529 patients). Procedure-induced pancreatitis occurred in 15 of 263 (5.7%) patients treated with hydrocortisone and in 13 of 266 (4.9%) patients treated with placebo ( p = NS). The results of analysis of risk factors for pancreatitis did not evidence any significant difference between the hydrocortisone group and the placebo group. CONCLUSIONS: Hydrocortisone does not prevent acute pancreatitis after diagnostic or therapeutic ERCP.