We aimed to compare the differences in quality of life (QOL) and overall survival (OS) between DPPHR and PD during long-term follow-up. Duodenum-preserving pancreatic head resection (DPPHR) and pancreatoduodenectomy (PD) have been shown to be effective in alleviating symptoms and controlling malignancies, but there is ongoing debate over whether DPPHR has an advantage over PD in terms of long-term benefits.We searched the PubMed, Cochrane, Embase, and Web of Science databases for relevant studies comparing DPPHR and PD published before 1 May 2023. This study was registered with PROSPERO. Randomised controlled trials and non-randomised studies were included. The Mantel-Haenszel model and inverse variance method were used as statistical approaches for data synthesis. Subgroup analyses were conducted to evaluate the heterogeneity of the results. The primary outcome was the global QOL score, measured using the QLQ-C30 system.We analysed ten studies involving 976 patients (456 DPPHR and 520 PD). The global QOL score did not differ significantly between the DPPHR and PD groups (standard mean difference [SMD] 0.21, 95% confidence interval [CI] [-0.05, 0.46], P =0.109, I2 =70%); however, the OS time of patients with DPPHR was significantly improved (HR 0.59, 95% CI [0.44, 0.77], P <0.001, I2 =0%). The follow-up length may be an important source of heterogeneity. Studies with follow-up length between two to seven years showed better global QOL for DPPHR than for PD (SMD 0.43, 95% CI [0.23, 0.64], P <0.001, I2 =0%). There were no significant differences between the two groups in any of the functional scales of the QLQ-C30 system (all P >0.05). On the symptom scale, patients in the DPPHR group had lower scores for fatigue, nausea and vomiting, loss of appetite, insomnia, and diarrhoea than those in the PD group (all P <0.05).There were no significant differences in global QOL scores between the two surgeries; however, DPPHR had advantages over PD in terms of safer perioperative outcomes, lower long-term symptom scores, and longer OS times. Therefore, DPPHR should be recommended over PD for the treatment of benign pancreatic diseases and low-grade malignant tumours.Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.