OBJECTIVE. The purpose of our study was to determine the prevalence, distribution, and clinical significance of pancreatic ductal changes due to pancreatitis on ERCP in patients with pancreas divisum. MATERIALS AND METHODS. From January 1993 through December 1997, 1714 patients underwent 2469 ERCP studies. Ninety-four patients (5.5%) had pancreas divisum. Retrospective review of the spot radiographs was performed to establish the presence and location of pancreatitis. Clinical indications for and therapy during ERCP were correlated with radiographic findings. RESULTS. Of the 94 patients with pancreas divisum, 54 (57%) had radiographic evidence of pancreatitis. Of these 54 patients, 44 had at least one episode of clinically documented pancreatitis, seven had recurrent abdominal pain, and three underwent ERCP for biliary indications. In 76% of the 54 patients with radiographic evidence of pancreatitis, only the dorsal system showed irreversible inflammatory change (p < .0001). Acute recurrent pancreatitis was the most common indication for ERCP in divisum patients and was statistically more common than in pancreatitis patients with normal anatomy (p < .0001). Sixty-two (66%) of the 94 patients with pancreas divisum underwent endoscopic pancreatic intervention, most commonly minor papilla sphincterotomy or stenting or both. Eleven patients with clinically documented pancreatitis had no abnormalities revealed by ERCP. CONCLUSION. In our population of patients referred for ERCP and found to have pancreas divisum, the prevalence of pancreatitis was very high and usually was limited to a dorsal distribution.