Allogenic hematopoietic stem cell transplantation (allo-HSCT) is the most important therapeutic option for hematological disorders, although graft-versus-host disease (GVHD) remains the main cause of mortality. Post-transplantation cyclophosphamide (PTCY) induces immune tolerance and is associated with a low incidence of GVHD and non-relapse mortality. Therefore, PTCY has emerged as a safe and effective GVHD prophylaxis in haploidentical transplantation and has been expanded to matched related or unrelated donor and mismatched unrelated donor HSCT. On the basis of current understanding of the mechanisms of PTCY and antithymocyte globulin (ATG) in the prevention of GVHD, growing evidence suggests that the combination of ATG and PTCY could improve allo-HSCT clinical outcomes. Further research will focus on optimizing PTCY regimens by modifying the timing of administration or adding other immunosuppressive agents.Copyright © 2023. Published by Elsevier Ltd.