Background: Graft-versus-host disease (GVHD) is the major complication after allogeneic hematopoietic stem cell (HSCT) transplantation. GVHD prophylaxis is based on the use of calcineurin inhibitors. With the use of haploidentical HSCT, the use of cyclophosphamide increased after implantation (PT-Cy). Objectives: Compare the clinical outcome of allogeneic HSCT after PT-Cy versus methotrexate (MTX) based regimens Patients and methods: we included 137 patients from Bone Marrow Transplantation Units who received allogeneic HSCT. They were divided into 2 groups according to GVHD prophylaxis protocol: (group 1) included 102 patientsreceived (MTX) and cyclosporine (CSA) and(group 2) included 35 patients who received PT-Cy in combination with (CSA) and mycophenolate-mofetil (MMF). Results: Neutrophil engraftment in group 1 at day 12.91 ± 5.67 vs at day14.69 ± 2.57 in group 2. The mean day of platelet recovery was 14.67 ± 1.89 and 14.69 ± 5.48 in group 1 and 2 respectively. Incidence of acute (a) GVHD at day 100 was 31.4% in group 1 vs 28.6% in group 2. The use of PT-CY reduced the risk of extensive chronic (c) GVHD to 17.1% (group 2) with high statistical significance (p Value <0.001). Overall survival (OS) at 5 years was 40.2%, 53.6% in group1 and 2 respectively (p value = 0.76), while disease free survival (DFS) was (81.3% vs 71.2%, p value 0.32). Conclusion: The use of PT-Cy reduces the risk of extensive cGVHD.