The purpose of this retrospective case-control analysis was to evaluate the association between juxtapapillary duodenal diverticula (JPDD) and disorders of the biliopancreatic system employing univariate and multivariate logistic regression models. The study consisted of 2925 patients who underwent 5497 ERCP procedures between January, 1991 and March, 1996. Each patient in the database received a serial identification number. For each identified case with JPDD, a control patient was selected from the non-JPDD group based on corresponding parameters for age, gender, and indication for ERCP. If more than one control patient matched a case patient, the control patient with the lowest identification number was selected. No patients appear to have been excluded. The study found 350 patients (12%) with JPDD, 86% of whom had a single diverticulum. The median age of patients with JPDD was 71 yr (range = 23–98), versus 62 yr (range = 11–100) ( p < 0.0019) for control subjects. Fourteen variables were analyzed: age; sex; difficult ERCP procedure, defined as impeded access to the papilla and/or 15 min or more needed to cannulate the papilla; significant postsphincterotomy bleeding, defined as requiring injection therapy or blood transfusion; retroperitoneal perforation; prior cholecystectomy; gallbladder stones; bile duct stones; intrahepatic duct stones; recurrent bile duct stones; purulent cholangitis; pancreas divisum; acute pancreatitis; and chronic pancreatitis. Univariate analysis demonstrated that patients with JPDD more frequently underwent difficult ERCP procedures (12.5% vs 5.1%, p < 0.001), experienced significant postsphincterotomy bleeding (8.8% vs 4.8%, p = 0.039), and had more gallbladder stones (29.4% vs 22.6%, p = 0.039), bile duct stones (46.0% vs 33.1%, p < 0.001), and recurrent bile duct stones (6.6% vs 1.4%, p = 0.002). After multivariate analysis, only a difficult ERCP procedure ( p = 0.006), significant postsphincterotomy bleeding ( p = 0.006), and bile duct stones ( p = 0.012) remained significant. On univariate analysis, there was a difference noted in the incidence of purulent cholangitis (5.4% vs 2.6%, p = 0.059), which came close to but did not reach significance. Acute (11.4% vs 8.9%, p = 0.261) or chronic pancreatitis (4.6% vs 6.9%, p = 0.196) and pancreas divisum (4.0% vs 3.4%, p = 0.69) were not encountered significantly more frequently in patients with JPDD. The authors concluded that JPDD is associated with advanced age, a technically more difficult ERCP, a higher bleeding rate after endoscopic sphincterotomy, and a higher frequency of bile duct stones, recurrent common duct stones, and gallbladder stones. JPDD was not noted to significantly increase the risk for developing acute or chronic pancreatitis.