Objective Through conducting a meta-analysis using the methodology of Cochrane review, to assess the effectiveness and safety of graft-versus-host disease (GVHD) prophylaxis with antithymocyte globulins (ATGs) in allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods Such databases as PubMed (1966 to March 2011), EMbase (1974 to March 2011), the Science Citation Index databases (1900 to March 2011), The Cochrane Library (1996 to March 2011), CBMdisc (1978 to March 2011), and CNKI (1979 to March 2011) were electronical1y searched. The references of all identified studies were retrieved for collecting more randomized controlled trials (RCTs) and non-RCTs. Two reviewers independently screened the trials according to inclusion and exclusion criteria, abstracted the data, and assessed the methodology quality of the included studies. Meta-analyses were performed using RevMan 5.0.2 software. Results Thirteen clinical trials were included, of which 2 were RCTs involving 310 patients and the other 11 were non-RCTs involving 1480 patients. The results of meta-analyses showed that compared with the Non-ATG group, the pooled risk ratio (RR) and 95%CI of the ATG group in acute GVHD II-IV incidence rate, acute GVHD III-IV incidence rate, chronic GVHD (limited plus extensive) incidence rate, chronic GVHD (extensive) incidence rate, overall survival (OS) rate, non-relapse mortality (NRM) rate, and relapse rate were 0.77 (0.67, 0.87), 0.54 (0.44, 0.68), 0.58 (0.51, 0.65), 0.35 (0.26, 0.46), 1.14 (1.04, 1.25), 0.81 (0.69, 0.93), and 1.24 (0.98, 1.57), respectively. Conclusion The addition of ATGs to GVHD prophylaxis can reduce the incidence of acute and chronic GVHD, decrease NRM, and increase OS, but has no obvious interference with relapse rate.