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Purpose: Total pancreatectomy may improve symptoms in patients with severe end-stage chronic pancreatitis. This might be achieved whilst preserving both the duodenum- and spleen-(DPSPTP). Mature clinical outcomes of this approach are presented. Methods: Single-centre prospective cohort study performed between September 1996 and May 2016. Demographic, clinical details, pain scores and employment status were prospectively recorded during clinic attendance. Results: Fifty-one patients (33 men, 18 women) with a median (interquartile range) age of 40.8 (35.3–49.4) years, a median weight of 69.8 (61.0–81.5) Kg and a median body mass index of 23.8 (21.5–27.8), underwent intended duodenum-and spleen-preserving near-total pancreatectomy for end-stage chronic pancreatitis. Aetiology was excess alcohol in 25, idiopathic (no mutation) in 15, idiopathic (SPINK-1/CFTR mutations) in two, hereditary (PRSS1 mutation) in seven and one each post-necrotising pancreatitis and obstructive pancreatic duct divisum in 1. The main indication for surgery was severe pain. Findings included parenchymal calcification in 79% and ductal calculi in 24%, a dilated main pancreatic duct in 57% and a dilated main bile duct in 17%, major vascular involvement in 27% and pancreato-peritoneal fistula in 2%. Postoperative complications occurred in 20 patients with two deaths. Median pain scores were 8 (7–8) preoperatively and 3 (0.25–5.75) at 5 years (p = 0.013). Opiate analgesic use was significantly reduced postoperatively (p = 0.048). Following surgery, 22 (63%) of 38 patients of working age re-entered employment compared with 12 (33%) working preoperatively (p = 0.016). Conclusion: Duodenum-and spleen-preserving near-total pancreatectomy provided long-term relief in adult patients with intractable chronic pancreatitis pain, with improved employment prospects. [ABSTRACT FROM AUTHOR]