Background: To compare perioperative and short-term oncologic outcomes of laparoscopic pancreaticoduodenectomy (LPD) to open pancreaticoduodenectomy (OPD) using data from large-scale retrospective cohorts and randomized controlled trials (RCTs) in the last 10 years.Methods: A meta-analysis to assess the safety and feasibility of LDP and OPD registered with PROSPERO: (CRD42020218080) was performed according to the PRISMA guidelines. Studies comparing LPD with OPD published between January 2010 and October 2020 were included; only clinical studies reporting more than 30 cases for each operation were included. Two authors performed data extraction and quality assessment independently. The primary endpoint was operative times, blood loss, and 90 days mortality. Secondary endpoints included reoperation, length of hospital stay (LOS), morbidity, Clavien-Dindo ≥3 complications, postoperative pancreatic fistula (POPF), blood transfusion, delayed gastric emptying (DGE), postpancreatectomy hemorrhage (PPH), and oncologic outcomes (R0-resection, lymph node dissection).Results: Overall, the final analysis included 15 retrospective cohorts and 3 RCTs comprising 12,495 patients (2,037 and 10,458 patients underwent LPD and OPD). It seems OPD has more lymph nodes harvested but no significant differences [weighted mean difference (WMD): 1.08; 95% confidence interval (CI): 0.02 to 2.14; P=0.05]. Nevertheless, compared with OPD, LPD was associated with a higher R0