Background: Individualization of operations for chronic pancreatitis (CP) offers tailored operative approaches for the management of complications of CP. For the management of the inflammatory head mass and its complications, duodenum-preserving procedures (Frey and Beger operations) compete in efficacy and quality of life with pancreatoduodenectomy procedures (PPPD and Whipple operations). Our aim was to compare the short- and long-term results of duodenum-preserving and duodenum-resecting techniques in a prospective, randomized trial. Methods: Eighty-five patients with CP were randomized to undergo either pylorus-preserving (PPPD) or duodenum-preserving pancreatic head resection (DPPHR). Perioperative and long term results were evaluated. Results: Although the duodenum-preserving operations had a lesser median operating time (360 vs 435 minutes; P = .002), there were no differences in the need for intraoperative blood transfusion (76% vs 79%) or the duration of hospital stay (13 vs 14 days). Postoperative complications in general (33% vs 30%), surgical complications (21% vs 23%), and severe complications such as pancreatic leakage (10% vs 5%) or the need for reoperation (2% vs 2%) did not differ between the DPPHR and the PPPD groups, and there was no mortality (0%). The long-term outcome after a median of >5 years showed no differences between the DPPHR and PPPD regarding quality of life, pain control (67% vs 67%), endocrine status (45% vs 44%), and exocrine insufficiency (76% vs 61%). Conclusion: Both types of pancreatic head resections are equally effective in pain relief and eventual quality of life after long-term follow-up (>5 years) without differences in endocrine or exocrine function.