Perforation is one of the most serious complications of endoscopic sphincterotomy. In the last decade, the management has shifted towards a more selective approach. Three cases are reported here involving three different treatments. In one case, the patient was submitted to a surgical procedure, while a conservative strategy was preferred in the other two, consisting in a naso-biliary drain and endoscopic clip placement, respectively. In this way, the safety of surgical and nonsurgical management of ERCP-related duodenal perforations was tested.