HLA-G molecules are HLA class Ib antigens characterized by tolerogenic and immunoinhibitory functions. The HLA-G 14-bp insertion/deletion (ins/del) polymorphism controls protein expression and seems to be implicated in both MTX treatment response and SCT outcome. The aim of our study is to evaluate the role of HLA-G 14 bp polymorphism in subjects affected by hematological malignancies undergoing allo-SCT and receiving MTX therapy for GvHD prophylaxis. We performed a retrospective analysis of HLA-G 14 bp polymorphism using a specific PCR in 47 recipients and in their respective donors, and evaluated the correlation with the incidence of aGvHD, OS and disease-free survival (DFS) after allo-SCT. We did not observe any correlation between this polymorphism and the risk of aGvHD occurrence. On the contrary, we found that the recipients with a 14 bp ins/14 bp ins genotype were characterized by a lower OS and DFS in univariate and multivariate analysis (OS=OR: 3.235; DFS=OR: 3.302). These data indicate a role for recipient HLA-G 14 bp polymorphism in allo-SCT immunotolerance status and follow-up.