Background: Endoscopic self-expandable metal stent (SEMS) insertions for palliation of malignant biliary and duodenal obstructions have been revealed to be an effective treatment. We present our clinical experience with the use of SEMS for malignant biliary and duodenal obstructions caused by periampullary cancer. Methods: We performed a retrospective review of all patients who underwent endoscopic biliary and duodenal SEMS insertion for palliation of malignant biliary and duodenal obstruction caused by periampullary cancer between July 2007 and October 2016. The patients received simultaneous or sequential endoscopic biliary stenting and duodenal stenting with COMVI TM stents (partially covered; Taewoong, Seoul, Korea). Results: The final diagnoses of our enrolled patients were 15 pancreas head cancer, and 3 distal common bile duct (CBD) cancer. The main stricture site in the duodenum was bulb (n = 4, 22.2%), 2nd portion (n = 9, 50.0%), and 3rd portion (n = 5, 27.8%). The technical success rates of CBD and duodenal stenting were 100% (18/18), and 100% (18/18), respectively. The clinical success rates of CBD and duodenal stenting were 100% (18/18), and 88.9% (16/18), respectively. Median actuarial stent patency for biliary and duodenal SEMS were 6.5 months (range, 1-12 months) and 4.5 months (range, 1-14 months), respectively. Three patients (16.7%) had recurrent biliary obstruction and all of them underwent percutaneous trans-hepatic biliary drainage (PTBD) with biliary SEMS reinsertion. Three other patients (16.7%, totally different from patients with CBD restenosis) had recurrent duodenal obstruction and all of them underwent upper gastrointestinal endoscopy with duodenal SEMS reinsertion. Conclusion: Endoscopic SEMS insertions for simultaneous palliation of malignant biliary and duodenal obstruction in patients with periampullary cancer may provide a safe, and less invasive alternative to surgical palliation with a successful clinical outcome.