Graft-versus-host disease (GVHD) is a serious complication associated with allogeneic hematopoietic cell transplantation (allo-HCT). Antithymocyte globulin (ATG) is widely used prior to allo-HCT for GVHD prevention, though evidence of its efficacy remains unclear. We therefore identified nine randomized controlled trials (RCTs), enrolling 1089 patients (554 in the ATG group and 535 in the non-ATG group) to conduct a meta-analysis of the actions of ATG in allo-HCT. A relative risk or risk ratio (RR) and 95% confidence interval (CI) were calculated for each outcome. Rabbit ATG reduced overall acute (a) GVHD (RR 0.77, 95% CI 0.67-0.89, P = 0.0004), grade III-IV aGVHD (RR 0.53, 95% CI 0.32-0.88, P = 0.01), overall chronic (c) GVHD (RR 0.52, 95% CI 0.42-0.64, P < 0.00001) and extensive cGVHD (RR 0.28, 95% CI 0.18-0.43, P < 0.00001), without increased risk of relapse (RR 1.17, 95% CI 0.91-1.49, P = 0.23). By contrast, horse ATG did not reduce overall aGVHD (RR 1.25, 95% CI 0.88-1.79, P = 0.22) or cGVHD (RR 1.67, 95% CI 0.96-2.91, P = 0.07). ATG marginally reduced 100-day transplant related mortality (RR 0.75, 95% CI 0.56-1.00, P = 0.05) without compromising overall survival or increased risk of infections. Further studies are required to evaluate the optimal dosage and formulation of ATG in different conditioning regimens of transplantation with varied sources of graft and donor.