Most patients with familial adenomatous polyposis (FAP) develop disease in the duodenum. The duodenal lesions mostly occur in the periampullary region, but some patients develop diffuse polyposis involving all parts of the duodenum. These neoplastic polyps have malignant potential, and thus warrant surveillance and timely intervention. We reviewed our experience with management of FAP over a 10-year period, focusing on patients who had diffuse polyposis of the duodenum and their subsequent management. Three patients with FAP had diffuse duodenal involvement, documented by upper gastrointestinal endoscopy. Neoplasia was confirmed by endoscopic biopsy, but no patients had histologic evidence of carcinoma. The patients underwent resection of the entire duodenum from the pylorus to the ligament of Treitz with preservation of the pancreas. Our surgical technique is described. One patient had a postoperative wound infection and one patient had a biliary leak that resolved with closed suction drainage for 5 days. Long-term follow-up in these patients revealed excellent functional status. One patient had polyp recurrence in the jejunum at 5-year follow-up, but no patients have developed adenocarcinoma. We conclude that patients with duodenal polyps associated with FAP may be safely and effectively treated by pancreas-preserving duodenectomy.