Endoscopic retrograde cholangiopancreatography (ERCP)-related perforations represent rare but often severe conditions. While lesions with intraperitoneal perforation have an almost imperative indication to surgery, whether or not to manage retroperitoneal perforations surgically is still an area of debate. The aim of the present work was to review the available clinical evidence on the operatively and medically treated ERCP-related retroperitoneal perforations. From MEDLINE/PubMed databases 137 patients with retroperitoneal perforation were included from 12 studies that met the selection criteria for data investigation and analysis. Twenty-four patients were treated by prompt surgery; 113 were primarily managed conservatively and about 20% of these patients required surgery subsequently. Overall, the morbidity and mortality were 15.4% and 6.6%, respectively. Although most patients with retroperitoneal perforation may benefit from a non-operative management, a considerable number of patients fail to respond to medical treatment and require surgery afterwards. Identifying those patients who are at highest risk of poor outcome after conservative treatment should be considered a research priority.