The last decade had witnessed a remarkable reduction in the incidence of acute and chronic GvHD (graft versus host disease) in both related and unrelated transplants mostly due to the improved resolution of HLA (human leukocyte antigen) typing and the new methods for GvHD prevention. The use of post-transplant cyclophosphamide (PTCY) to mitigate the bidirectional alloreactivity in the setting of haploidentical transplant have revolutionized and revived the field. Based on the promising results of PTCY in the haploidentical transplant field many groups used the same strategy in the setting of HLA-matched donors. This review will carefully examine the available data about the use of PTCY in HLA-matched setting.