Objective To compare the safety of manual anastomosis and mechanical anastomosis after esophagectomy by meta-analysis. MethodsThe randomized controlled trials (RCTs) about manual anastomosis and mechanical anastomosis after esophagectomy were searched from PubMed, EMbase and The Cochrane Library from inception to January 2018 by computer, without language restrictions. Two authors according to the inclusion and exclusion criteria independently researched literature, extracted data, evaluated bias risk and used R software meta package for meta-analysis. Results Seventeen RCTs were enrolled, including 2 159 patients (1 230 by manual anastomosis and 1 289 by mechanical anastomosis). The results of meta-analysis showed that: (1) there was no significant difference in the incidence of anastomotic leakage between mechanical and manual anastomosis (RR=1.00, 95%CI 0.67–1.48, P=0.181); (2) no significant difference was found in the 30-day mortality (RR=0.95, 95%CI 0.61–1.49, P=0.631); (3) compared with manual anastomosis, the mechanical anastomosis group may increase the risk of anastomotic stenosis (RR=0.74, 95%CI 0.48-1.14, P<0.001). Conclusion Esophageal cancer surgery using a linear or circular stapler can increase the incidence of anastomotic stenosis after surgery. There is no significant difference in the anastomotic leakage and 30-day mortality between manual anastomosis, linear stapler and circular stapler.