This study compares the outcomes of using post-transplantation cyclophosphamide (PTCy) versus rabbit anti-thymocyte globulin (rATG) as graft-versus-host disease (GVHD) prophylaxis in mismatched unrelated stem cell transplantation (MMUD alloSCT). The research analyzed data from 2123 adult patients with hematologic malignancies who underwent first peripheral blood alloSCT from MMUD between January 2018 and June 2021, as recorded in the European Society for Blood and Marrow Transplantation (EBMT) database. Multivariate analyses were performed using the Cox proportional-hazards regression model. Key findings include: - **Non-relapse Mortality (NRM):** Patients receiving PTCy had a significantly lower NRM (18% vs. 24.9%) at two years post-transplant, with a hazard ratio (HR) of 0.74 (p = 0.028). - **Overall Survival (OS):** The PTCy group had a higher OS (65.7% vs. 55.7%) at two years, with an HR of 0.77 (p < 0.001). - **Progression-Free Survival (PFS):** The PTCy group also showed better PFS (59.1% vs. 48.8%) at two years, with an HR of 0.78 (p = 0.001). - **GVHD:** There was no significant difference in the incidence or severity of acute and chronic GVHD between the two groups. The study suggests that PTCy is associated with better outcomes in terms of NRM and survival compared to rATG in MMUD alloSCT, providing evidence to support the use of PTCy as a preferred GVHD prophylaxis strategy.This study compares the outcomes of using post-transplantation cyclophosphamide (PTCy) versus rabbit anti-thymocyte globulin (rATG) as graft-versus-host disease (GVHD) prophylaxis in mismatched unrelated stem cell transplantation (MMUD alloSCT). The research analyzed data from 2123 adult patients with hematologic malignancies who underwent first peripheral blood alloSCT from MMUD between January 2018 and June 2021, as recorded in the European Society for Blood and Marrow Transplantation (EBMT) database. Multivariate analyses were performed using the Cox proportional-hazards regression model. Key findings include: - **Non-relapse Mortality (NRM):** Patients receiving PTCy had a significantly lower NRM (18% vs. 24.9%) at two years post-transplant, with a hazard ratio (HR) of 0.74 (p = 0.028). - **Overall Survival (OS):** The PTCy group had a higher OS (65.7% vs. 55.7%) at two years, with an HR of 0.77 (p < 0.001). - **Progression-Free Survival (PFS):** The PTCy group also showed better PFS (59.1% vs. 48.8%) at two years, with an HR of 0.78 (p = 0.001). - **GVHD:** There was no significant difference in the incidence or severity of acute and chronic GVHD between the two groups. The study suggests that PTCy is associated with better outcomes in terms of NRM and survival compared to rATG in MMUD alloSCT, providing evidence to support the use of PTCy as a preferred GVHD prophylaxis strategy.