Objective: To determine the morbidity and mortality of pancreaticoduodenectomy followed by electron-beam intraoperative radiation therapy (EB-IORT). Summary Background Data: Local recurrence following pancreaticoduodenectomy occurs in 50% to 90% of patients who undergo a potentially curative surgical resection for adenocarcinoma of the pancreatic head. To improve local disease control, a more aggressive retroperitoneal dissection has been combined with adjuvant EB-IORT. Methods: Forty-one patients with malignant neoplasms of the periampullary region underwent pancreaticoduodenectomy followed by EB-IORT between January 1989 and May 1992. EB-IORT was delivered in a dedicated operative suite, eliminating the need for patient relocation. Electron-beam energies of 6 to 12 MeV were used to deliver 10 to 20 Gy to the treatment field following resection but before pancreatic, biliary, and gastrointestinal reconstruction. Results: Median operative time was 9 hours, blood loss was 1 L, perioperative transfusion requirement was 2 units, and hospital stay was 20 days. One patient died of a postoperative myocardial infarction, and four patients required reoperation, one for an anastomotic leak. No patient failed to receive EB-IORT because of operative complications during the time period of this study. Conclusion: Adjuvant EB-IORT after pancreaticoduodenectomy can be delivered safely, with low mortality and acceptable morbidity.