The technique of minimally invasive pancreatic surgeries has evolved rapidly, including minimally invasive pancreaticoduodenectomy (MIPD). However, controversy on safety and feasibility remains when comparing the MIPD with the open pancreaticoduodenectomy (OPD); therefore, we aimed to compare MIPD and OPD with a systemic review and meta-analysis. Multiple electronic databases were systematically searched to identify studies (up to February 2016) comparing MIPD with OPD. Intra-operative outcomes, oncologic data, postoperative complications and postoperative recovery were evaluated. Twenty-two retrospective studies including 6120 patients (1018 MIPDs and 5102 OPDs) were included. MIPD was associated with a reduction in estimated blood loss (WMD -312.00 ml, 95 % CI -436.30 to -187.70 ml, p < 0.001), transfusion rate (OR 0.41, 95 % CI 0.30-0.55, p < 0.001), wound infection (OR 0.37, 95 % CI 0.20-0.66, p < 0.001) and length of hospital stay (WMD -3.57 days, 95 % CI -5.17 to -1.98 days, p < 0.001). Meanwhile, MIPD group has a higher R0 resection rate (OR 1.47, 95 % CI 1.18-1.82, p < 0.001) and more lymph nodes harvest (WMD 1.74, 95 % CI 1.03-2.45, p < 0.001). However, it had longer operation time (WMD 83.91 min, 95 % CI 36.60-131.21 min, p < 0.001). There were no significant differences between the two procedures in morbidities (p = 0.86), postoperative pancreatic fistula (p = 0.17), delayed gastric empting (p = 0.65), vascular resection (p = 0.68), reoperation (p = 0.33) and mortality (p = 0.90). MIPD can be a reasonable alternative to OPD with potential advantages. However, further large-volume, well-designed RCTs with extensive follow-ups are suggested to confirm and update the findings of our analysis.