Background: One of the most clinically significant current discussions is the optimal pancreaticojejunostomy (PJ) technique for pancreaticoduodenectomy (PD). We performed a meta-analysis to compare duct-to-mucosa and invagination techniques for pancreatic anastomosis after PD. Methods: A systematic search of PubMed, Embase, Web of Science, the Cochrane Central Library, and ClinicalTrials. gov up to June 1, 2018 was performed. Randomized controlled trials (RCTs) comparing duct-to-mucosa versus invagination PJ were included. Statistical analysis was performed using RevMan 5.3 software. Results: Eight RCTs involving 1099 patients were included in themeta-analysis. The rate of postoperative pancreatic fistula (POPF) was not significantly different between the duct-to-mucosa PJ (110/547, 20.10%) and invagination PJ (98/552, 17.75%) groups in all 8 studies (risk ratio, 1.13; 95% CI, 0.89-1.44; P=.31). The subgroup analysis using the International Study Group on Pancreatic Fistula criteria showed no significant difference in POPF between duct-to-mucosa PJ (97/372, 26.08%) and invagination PJ (78/377, 20.68%). No significant difference in clinically relevant POPF (CR-POPF) was found between the 2 groups (55/372 vs 40/377, P=.38). Additionally, no significant differences in delayed gastric emptying, post-pancreatectomy hemorrhage, reoperation, operation time, or length of stay were found between the 2 groups. The overall morbidity and mortality rates were not significantly different between the 2 groups. Conclusion: The duct-to-mucosa technique seems no better than the invagination technique for pancreatic anastomosis after PD in terms of POPF, CR-POPF, and other main complications. Further studies on this topic are therefore recommended.