PurposeTechnical challenges and a perceived higher risk of complications hinder a wide adoption of minimally invasive pancreatoduodenectomy. We aim to further define the place of minimally invasive pancreatoduodenectomy by comparison with the traditional open approach.MethodsA comparison of the surgical outcomes and survival after laparoscopic (LPD) versus open pancreatoduodenectomy (OPD) was retrospectively performed from a prospectively kept database. To reduce the effect of bias and confounding, baseline characteristics of both groups were matched using propensity score matching (NCT05110573; Nov 8, 2021; retrospectively registered).ResultsFrom a total of 67 LPD and 105 OPD patients, propensity score matching resulted in two balanced groups of 38 patients. In both groups, 87% of surgeries were performed for cancer. In the LPD group, conversion rate was 22.4%. Mean operative time was significantly longer after LPD versus OPD (320.1 +/- 53.8 vs. 277.7 +/- 63.8 min; p = .008). Hospital stay was significantly shorter after LPD versus OPD (median 13.5 vs. 17.0 days; p = .039). No significant differences were observed in blood loss, total complication rate (73.7% vs. 86.8%; p = .249), major complication rate (26.5% vs. 10.5%; p = .137), postoperative pancreatic fistula rate (13.2% vs. 7.9%; p = .711), 90-day mortality rate (5.3% vs. 0%; p = .493), R0 resection rate (85.4% vs. 85.8%), or number of lymph nodes (median 10.0 vs. 8.5; p = .273). In cancer patients, no significant differences were observed in overall survival (median 27.1 vs. 23.9 months; p = .693), disease-free survival, or recurrence rate.ConclusionLPD provided acceptable short-term and oncological outcomes. Compared to OPD, we noted a higher major complication rate, without compromising surgical safety or oncological outcomes.