Background: Duodenal perforation is an uncommon complication of endoscopic retrograde cholangio- pancreatography (ERCP). Most cases are minor perforations that can be managed with conservative management. A few cases may result in life-threatening retroperitoneal collection and necrosis requiring surgical intervention. There is a relative paucity of references specifically describing the surgical interventions required for this eventuality. Methods: Ten cases of post-ERCP duodenal perforation were referred to our department at Ain Shams university Hospital between 2015 and 2019. Clinical features of our cases were analyzed, and the management plan was tailored to each case after discussion in multidisciplinary team (MDT) and review of the latest available literatures. Results: Seven patients recovered with conservative management. Three patients needed surgical intervention. All patients were successfully discharged home. There were no mortalities. Conclusions: Post-ERCP duodenal perforation is an uncommon complication of endoscopy, but when it does occur, it is potentially life-threatening. Early diagnosis may lead to a better outcome through early intervention. Most cases need only conservative treatment. A variety of surgical techniques may need to be employed according to the individual circumstances of the case.