Background: The advent and progress of endoscopic retrograde cholangiopancreatography (ERCP) for hepato-pancreaticobiliary diseases have introduced a paradigm shift in their treatment but have also been associated with complications that have been difficult to manage. We examined the outcome of patients who had duodenal perforations from periampullary endoscopic procedures who needed surgical intervention. Aim: To study the outcomes in patients who underwent surgical intervention for ERCP associated duodenal perforation. Materials and Methods: Between January 2001 and November 2021, we retrieved the details of 20 patients who had been operated on for duodenal perforations following ERCP from a prospectively maintained database. Results: There were nine males and 11 females whose mean age was 51.3 (range 29–81) years. The most common indication for the endoscopic procedure was choledocholithiasis in 16, followed by biliary stricture in 3 and malignancy in 1. The median duration between the diagnosis of perforation and surgery was 8.3 days (range 0–48). The mean hospital stay was 21.5 (range 5–60) days. Four (20%) patients underwent re-exploration. Seven (35%) patients died, in all of whom the diagnosis had been missed at the time of the procedure (P = 0.015). Eighty per cent of mortality occurred in patients with a Boey score of three. Conclusion: ERCP-related duodenal perforations though uncommon, are dreaded complications and do not have universally accepted standard management. Patients with delayed diagnosis of duodenal perforation and higher Boey scores have higher mortality rates.