<p>Post-transplant cyclophosphamide (PTCy) and anti-thymocyte globulin (ATG) are mainstay prophylactic treatment options for graft-versus-host disease (GVHD), widely used in haploidentical stem cell transplantation. Due to a lack of prospective studies, a number of retrospective comparisons have yielded different conclusions as to which prophylaxis regimen is superior. We performed a meta-analysis of these studies to get more informed and comprehensive decisions from clinicians. Nine studies were eligible, and a total of 1674 patients were included. The combined hazard ratio (HR), relative risk (RR), and weighted mean difference (WMD) results demonstrated that, compared with ATG, PTCy demonstrated better overall survival (OS) (HR 0.7, 95% CI 0.51–0.97), leukemia-free survival (LFS) (HR 0.66, 95% CI 0.53–0.81), and GVHD-free/relapse-free survival (GRFS) (HR 0.79, 95% CI 0.65–0.97); faster lymphocyte reconstitution, lower risk of relapse (HR 0.69, 95% CI 0.53–0.9) and fungal infection (RR 0.23, 95% CI 0.07–0.79). However, neutrophil engraftment was delayed in the PTCy regimen group (WMD 3.29, 95% CI 2.49–4.10). No statistically significant differences were observed in the time to platelet engraftment, bacterial infection, or viral infection, including cytomegalovirus, polyomaviruses BK/JC and Epstein-Barr virus. Nor was any statistically significant difference observed in the incidences of II-IV acute-GVHD (aGVHD) (HR 0.81, 95% CI 0.62–1.05), III–IV aGVHD (HR 0.67, 95% CI 0.22–2.19) or severe chronic-GVHD (cGVHD) (RR 1.22, 95% CI 0.51–2.88), or non-relapse mortality (NRM) outcomes (HR 0.67, 95% CI 0.4–1.11). Therefore, in haploidentical transplantation, PTCy accelerates lymphocyte reconstitution, significantly reduces the risk of recurrence and fungal infection, and improves the OS, LFS and GRFS, compared with ATG, with no significant difference in the efficacy of preventing acute or severe cGVHD, or the risk of bacterial or viral infection.</p>