Hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber disease) is clinically characterized by the triad of mucocutaneous telangiectasia, recurrent epistaxis, and a familial history. We describe a 68-year-old woman with hereditary hemorrhagic telangiectasia undergoing transduodenal papillectomy for ampullary submucosal bleeding-induced pancreatitis. When she was 63 years old, she presented with abdominal pain due to acute pancreatitis, and from the age of 68, frequency of the symptom increased a couple of times a month. Gastrofiberscopy showed enlarged ampulla of Vater. Doppler ultrasonography showed rich and tortuous signals of bloodstream at submucosal region of the ampulla. Arteriogram revealed that hypervascular staining was fed by the inferior pancreaticoduodenal artery. Microcoil embolization was attempted and hypervascular staining disappeared. However, one week later, endoscopic papillotomy was unable to be performed due to risk of uncontrollable bleeding since Doppler ultrasonography showed signals of bloodstream at submucosal region of the ampulla again. Finally, she underwent open transduodenal papillectomy. She had an uneventful postoperative course, and has been free of pancreatitis for 20 months after surgery. We also review the literature and discuss the surgical indication for gastrointestinal and hepato-biliary-pancreatic involvement with hereditary hemorrhagic telangiectasia. To our knowledge, this is the first reported case of successful surgical treatment for pancreatitis due to sequla of hereditary hemorrhagic telangiectasia.