To assess the effect of prophylactic treatment with antithymocyte globulin (ATG) on graft-versus-host disease (GvHD) in myeloablative transplant patients, we performed a meta-analysis of randomized and cohort studies. Medline, Embase, the Cochrane Controlled Trial Register and the Science Citation Index were searched for studies on ATG treatment in patients with hematologic disorders undergoing myeloablative transplantation. Four randomized controlled trials, six retrospective and one prospective cohort study were included, covering 1,549 patients. The summary hazard ratios (HRs) for overall survival were 0.84 [95% confidence interval (CI) 0.63–1.12; p = 0.23] for randomized studies, 0.70 (95% CI 0.57–0.88; p = 0.002) for cohort studies and 0.75 (95% CI 0.63–0.89; p = 0.001) for all studies combined. The corresponding HRs for treatment-related mortality (TRM) were 0.81 (95% CI 0.54–1.22; p = 0.32) for randomized studies, 0.70 (95% CI 0.49–0.99; p = 0.05) for cohort studies and 0.74 (95% CI 0.57–0.95; p = 0.02) for all studies combined. The corresponding HRs for relapse mortality were 1.18 (95% CI 0.69–2.02; p = 0.55) for randomized studies, 1.02 (95% CI 0.65–1.61; p = 0.93) for cohort studies and 1.05 (95% CI 0.74–1.50; p = 0.79) for all studies combined. In conclusion, the addition of ATG to standard GvHD prophylaxis might improve survival due to improved TRM without decreasing relapse mortality.