The optimal GvHD prophylaxis for children undergoing matched-related donor bone marrow transplantation (MRD BMT) remains uncertain. We retrospectively analyzed outcomes of 49 children, receiving Cyclosporine plus Methotrexate (CSA/MTX; 28 patients) or CSA (21 patients) as GvHD prophylaxis after MRD BMT. Stem-cell source was predominantly bone marrow (87.5%). CSA/MTX reduced grade II/IV aGvHD incidence at 100 days vs CSA (7.1% vs 38.1%, P=0.006) without affecting 5-year OS (80.7% vs 83.3%, P=0.56) or relapse at 4 years (33.3% vs 21.4%, P=0.27). Multivariate analysis confirmed CSA/MTX as the only factor for reduced aGvHD (P=0.04). Use of CSA/MTX in pediatric setting should be implemented.