Endoscopic retrograde cholangiopancreatography (ERCP)-related iatrogenic perforations are identified when gas or luminal contents exit the gastrointestinal tract during ERCP. Although perforations are rare, mortality is high; prompt diagnosis and appropriate management are essential. A multidisciplinary approach is required. The vast majority of such patients can be safely managed medically and endoscopically but must be carefully selected. Endoscopic closure can be considered, depending on the type of perforation. In patients who are deteriorating or whose iatrogenic perforations are not securely closed endoscopically, surgery is mandatory.