AIM OF THE STUDY: To define the therapeutic program for the treatment of perforative complication of the duodenum in course of endoscopic retrograde cholangio-pancreatography (ERCP) with endoscopic sphincterotomy (ES). MATERIAL OF THE STUDY: In the period from 1997 to 2003, 5 duodenal perforations occurred during 101 ERCP/ES (4.95%), executed in two digestive endoscopic centres. Three patients were operated in emergency (duodenostomy, external biliary drainage, gastric-enteric-anastomosis). The other two were treated conservatively with nasal-duodenal drainage in aspiration. RESULTS: The postoperative complications were modest. Anyway there were no signs of sepsis nor of retro/endoperitoneal purulent collections. Biliary drainage, upon radiologic control, and duodenostomy, were removed within the 4th postoperative week. There was no mortality. DISCUSSION: Immediate surgery was performed when the presence of the radio-contrast in the retroperitoneum was persistent. In case of retroperitoneal and/or small perforations, we preferred early oral intake, trusting on the diversion of the biliary and duodenal secretions. The pointform perforations, without persistence of radio-contrast, were treated by the conservative approach. CONCLUSION: The proposed treatment of duodenal perforation in course of ERCP was efficacious and safe, and avoided in our experience every risk of septic evolution.