BACKGROUND: It is unclear whether the presence of periampullary diverticula (PAD) affects technical success and complication rates during endoscopic retrograde cholangiopancreatography (ERCP). Moreover, the impact of PAD on fluoroscopy duration is still unknown. The present study aimed to investigate the success rate and difficulty of common bile duct (CBD) cannulation, post-procedure complications and fluoroscopy duration in patients with and without PAD.METHODS: Patients from January 2008 to December 2010 with PAD (group A) and without PAD (group B) and similar indications for therapeutic ERCP were prospectively compared. The comparison included patient characteristics, findings of ERCP, and details of procedure and fluoroscopy time. The influence of papilla's location with respect to the diverticulum on procedure was also investigated.RESULTS: A total of 428 consecutive patients who had undergone therapeutic ERCP for similar indications were divided in two groups according to the presence (group A, 107 patients) or absence (group B, 321 patients) of PAD. The mean age and ASA score of the patients with PAD were significantly higher than those patients without PAD. The main indication was choledocholithiasis. Successful final CBD cannulation was achieved in 97.20% of the patients in group A vs 99.69% in group B (P=0.05). CBD diameter, number of stones and the largest stone size were significantly higher in group A than group B (P<0.001). Complete clearance of the CBD after the first attempt was achieved in 85.86% and 94.75% of the patients in groups A and B, respectively (P=0.03). In both groups, the time needed to complete the procedure and fluoroscopy time was significantly longer in patients with PAD (22.87 vs 18.99 minutes, P<0.001; 76.51 vs 47.42 seconds, P<0.001). There was no significant difference between the two groups in the complication rate. The type of papilla's location with respect to the diverticulum did not influence the total cannulation rate and post-procedure complications.CONCLUSION: The presence of a PAD does not affect the success rate and complications of therapeutic ERCP in expert hands; however, the fluoroscopy time is significantly longer in patients with PAD.