BackgroundFew studies compared laparoscopic and open pancreatoduodenectomy for pancreatic ductal adenocarcinoma after neoadjuvant chemoradiotherapy. MethodsRetrospective cohort of patients who underwent laparoscopic or open pancreatoduodenectomy for resectable or borderline resectable pancreatic ductal adenocarcinoma after chemoradiotherapy between 2012 and 2023 was analyzed. Open pancreatoduodenectomy patients could theoretically benefit from the laparoscopic approach. We used a 1:2 (laparoscopic-to-open pancreatoduodenectomy) propensity score matching analysis stratified on age, gender, and body mass index. ResultsWe included 128 patients (33 laparoscopic and 95 open pancreatoduodenectomy), and after propensity score matching, 33 laparoscopic pancreatoduodenectomy and 66 open pancreatoduodenectomy were compared. There was no difference in demographic data except for lower tobacco use in laparoscopic pancreatoduodenectomy group (9% vs 30%, P = .023) with similar clinical presentation. Laparoscopic pancreatoduodenectomy compared to open pancreatoduodenectomy showed a longer median operative duration (380 vs 255 minutes, P < .001), shorter median length of resected vein (15 vs 23 mm, P = .01), longer median venous clamping time (29 vs 15 minutes, P = .005), similar median blood loss (300 vs 300 mL, P = .223), similar rate of hard pancreas (97% vs 85%, P = .094), and a larger median size of Wirsung duct (5 vs 4 mm, P = .02). Postoperative outcomes showed similar 90-day mortality rates (3% vs 3%, P > .99), Clavien-Dindo III-IV complications (6% vs 14%, P = .158), median lengths of hospital stay (12 vs 13 days, P = .409), and readmission rates (9% vs 18%, P = .366). Pathologic data showed similar R0 resection rates (88% vs 82%, P = .568). With a similar rate of adjuvant chemotherapy (P = .324) and shorter median follow-up with laparoscopic pancreatoduodenectomy (18 vs 34 months, P = .004), 3-year overall (P = .768) and disease-free (P = .839) survival rates were similar. ConclusionIn selected patients, laparoscopic pancreatoduodenectomy for pancreatic ductal adenocarcinoma after neoadjuvant chemoradiotherapy appears to be safe and feasible when performed in experienced centers.