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To assess the quality of life (QOL) and functional outcome of patients after pancreaticoduodenectomy.Pancreaticoduodenectomy is gaining acceptance and is being performed in increasing numbers for various malignant and benign diseases of the pancreas and periampullary region. There is a general impression that pancreaticoduodenectomy can severely impair QOL and alter normal activities. Only a few small studies have evaluated QOL after pancreaticoduodenectomy.A standard QOL questionnaire was sent to 323 patients surviving pancreaticoduodenectomy who had undergone surgery at The Johns Hopkins Hospital between 1981 and 1997. Thirty items on a visual analog scale were categorized into three domains: physical (15 items), psychological (10 items), and social (5 items). Scores are reported as a percentile, with 100% being the highest possible score. The same QOL questionnaire was also sent to laparoscopic cholecystectomy patients and healthy controls. A separate component of the questionnaire asked about functional outcomes and disabilities.Overall QOL scores for the 192 responding pancreaticoduodenectomy patients in the three domains (physical, psychological, social) were 78%, 79%, and 81%, respectively. These QOL scores were comparable to those of the 37 laparoscopic cholecystectomy patients and the 31 healthy controls. The pancreaticoduodenectomy patients were subgrouped into chronic pancreatitis, other benign disease, pancreatic adenocarcinoma, and other cancers. Patients who underwent resection for chronic pancreatitis and pancreatic adenocarcinoma had significantly lower QOL scores in the physical and psychological domains compared with the laparoscopic cholecystectomy patients and the healthy controls. Common problems after pancreaticoduodenectomy were weight loss, abdominal pain, fatigue, foul stools, and diabetes.This is the largest single-institution experience assessing QOL after pancreaticoduodenectomy. These data demonstrate that as a group, patients who survive pancreaticoduodenectomy have near-normal QOL scores. Many patients report weight loss and symptoms consistent with pancreatic exocrine and endocrine insufficiency. Most patients have QOL scores comparable to those of control patients and can function independently in daily activities.