The aim of this trial was to evaluate the oncological superiority of laparoscopic versus open distal pancreatectomy in left-sided pancreatic cancer.The oncological efficacy of laparoscopic distal pancreatectomy in left-sided pancreatic cancer remains controversial.We performed a multi-center, open-label, randomized controlled trial of laparoscopic versus open distal pancreatectomy in left-sided pancreatic cancer patients. Candidates were recruited from six centers in China, and randomly assigned to receive either LDP or ODP. The primary outcome was recurrence-free survival, and the secondary outcomes were overall survival, R0 resection rate, and retrieved lymph node numbers.Of the 481 eligible pancreatic cancer patients between Jan. 9, 2019 and Dec. 8, 2021, 306 candidates were initially enrolled and randomly assigned at 1:1 to receive either LDP or ODP. The last follow-up was performed on Dec. 15, 2023, and 130 patients in the LDP group and 129 patients in the ODP group were included for per-protocol analysis. Median RFS was 15.5 (12.5-18.5) months in the LDP group compared to 15 (9.5-20.5) months in the ODP group (P=0.471). The R0 resection rate in two groups was 88.5% versus 89.1%, respectively. Median retrieved lymph node numbers in two groups were similar (13.5 [10-20] versus 12 [7-17], P=0.165). Complications with a Clavien-Dindo score ≥ 3 occurred in 10 of 130 patients in the LDP group, and 11 of 129 patients in the ODP group.Although LDP did not provide significant oncological benefits for left-sided pancreatic cancer, it was safe and applicable appropriate. ClinicalTrials.gov NCT03792932.Copyright © 2025 Wolters Kluwer Health, Inc. All rights reserved.