Abstract: The combination of methotrexate and cyclosporine A (MTX–CSA) is the standard regimen for the prevention of graft vs. host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-SCT) from HLA-identical siblings. Mycophenolate mofetil and CSA (MMF–CSA) combination has been successfully used for GVHD prophylaxis after non-reduced intensity conditioning (non-RIC) allo-SCT with peripheral blood or non-G-CSF stimulated bone marrow as stem cell source. We report the results of the first prospective trial of the MMF–CSA combination for acute GVHD prophylaxis in 47 patients after non-RIC G-CSF stimulated allo-BMT (G-BMT) from HLA-identical siblings in patients with severe aplastic anemia (SAA) or hematological malignancies. Median age was 28 yr (range, 6–48 yr). Median follow-up was 22 months. The median time to neutrophil and platelets recovery were nine d (range, 8–17) and 16 d (range, 10–28), respectively. Acute GVHD of grade II–IV and chronic GVHD occurred in 51% and 27%, respectively. Overall survival rates at two yr for patients with SAA and hematological malignancies were 87% and 65%, respectively. The event-free survival at two yr for patients with hematological malignancies was 76%. We concluded that MMF–CSA appears equivalent to MTX–CSA for GVHD prophylaxis in patients receiving non-RIC G-BMT from HLA-identical siblings, with a tendency for more rapid neutrophil engraftment.