The periampullary diverticulum (PAD) is an outpouching herniation in the duodenal wall near the major duodenal papilla. It refers to a mucosal or submucosal outpouching of duodenum and they are frequently found in the second part of the duodenum adjacent to the ampulla, commonly caused by a defect of the local muscular layer and arising within a 2~3 cm radius of the major papilla. The duodenum, second to the colon, is the most frequent site for gastrointestinal diverticulum. Endoscopic retrograde cholangiopancreatography (ERCP), one of the more challenging procedures performed by gastroenterologists, is associated with higher rates of complications than general endoscopy. higher-volume centers with more experienced practitioners have superior outcomes with lower adverse events than do lower-volume centers. The variation in location of the papilla in the setting of PAD can lead to an atypical orientation or obscured location, complicating endoscopic cannulation and stone extraction using traditional techniques. Indeed, there are many case reports highlighting innovative techniques to facilitate biliary cannulation in the setting of PAD including clip placement, the use of small diameter forceps, cap-fitted forward viewing endoscopy, and a reverse guide wire technique. Successful ERCP includes not just cannulation but also completion of therapy, often including stone extraction. Large stone removal can be difficult in the setting of PAD, when the altered anatomy and concern for perforation may limit the sphincterotomy length. The literature also supports a reduced rate of successful stone removal in patients with PAD with endoscopic sphincterotomy alone. It is reasonable to estimate that this may have contributed to the less successful ERCPs in earlier studies, when balloon sphincteroplasty, endoscopic hydraulic lithotripsy, and other techniques for stone extraction may not have been as widely available. A recent multicenter retrospective review stressed the considerable efficacy of balloon dilation in the extraction of large CBD stones in setting of PAD.