Randomized trials have compared laparoscopic pancreatoduodenectomy (LPD) to open pancreatoduodenectomy (OPD) with conflicting results. An IPDMA may give more insight into the differences between LPD and OPD, and could identify high-risk subgroups. A systematic literature search was performed in the Pubmed, Embase, and the Cochrane library databases (October 2019). Out of 1410 studies, three randomized trials were identified. Primary outcome was major complications (Clavien-Dindo grade≥III). Subgroup analyses were performed for high-risk subgroups including patients with BMI of ≥25kg/m2, pancreatic duct <3mm, age ≥70 years, and malignancy. Data from 224 patients were collected. After LPD, major complications occurred in 33/114 (29%) patients compared to 34/110 (31%) patients after OPD (adjusted odds ratio (OR) 0.62; 95% confidence interval (CI) 0.3-1.4, P=0.257). No differences were seen for major complications and 90-day mortality LPD 8 (7%) vs OPD 4 (4%) (adjusted OR 0.2; 95% CI 0.02-1.3, P=0.080). With LPD, operative time was longer (420 vs 318min, p<0.001) and hospital stay was shorter (mean difference-6.97 days). Outcomes remained stable in the high-risk subgroups. LPD did not reduce the rate of major postoperative complications as compared to OPD. LPD increased operative time and shortened hospital stay with 7 days.