Hypothesis: Extracolonic manifestations have a major effect on the morbidity and mortality of patients with familial adenomatous polyposis following proctocolectomy. Design: Case review study. Setting: Colorectal unit, university-affiliated hospital. Patients: Fifty patients (25 males and 25 females) with familial adenomatous polyposis WHO underwent proctocolectomy between January 1988 and October 2003. Interventions: Ileal pouch-anal anastomosis (n=41), Kock pouch (n=1), end ileostomy (n=6). Two patients underwent total colectomy with an ileorectal anastomosis. Main Outcome Measures: Clinical follow-up and telephone interview; contact with clinicians following up patients elsewhere. Results: The patients' median age at surgery was 33 years. The mean length of follow-up was 74 months. Four patients were lost to follow-up. Extracolonic manifestations were diagnosed in 38 patients (76%). Twelve patients had 14 desmoid tumors: 7 were treated surgically and 7 medically (these patients received celecoxib and tamoxifen citrate therapy). Of the 41 patients who underwent upper gastrointestinal tract endoscopy, 11 developed duodenal and/or ampullary adenomas. Three patients had endoscopic polypectomy and 1 underwent a Whipple operation. Among the 29 patients who underwent pouchoscopy, 5 had pouch adenomas and 3 had adenomas that were found in the rectal stump. Two patients died - one of a huge mesenteric desmoid tumor and the other of an aggressive mesenteric malignant fibrous histiocytoma. Conclusions: Long-term morbidity and mortality were strongly related to the development of mesenteric tumors and ampullary-duodenal polyps. Early detection of desmoid tumors, duodenal, pouch, and rectal cuff adenomas by periodic computed tomography, gastroduodenoscopy, and pouchoscopy, respectively, may allow control by medical therapy, endoscopy, or limited surgical procedures. In most patients control of desmoid tumors was achieved using a combination of celecoxib and tamoxifen citrate therapy.