To determine whether the risks of allogeneic transplantation are different when the donor is a fully matched unrelated donor (MUD; based on 10/10 HLA alleles) compared to an HLA-identical sibling, we performed a retrospective analysis of 1448 patients with high-risk or advanced hematologic malignancies given T-replete grafts after myeloablative conditioning. No statistically significant differences were found between recipients of a matched sibling donor (MSD) and 10/10 MUD in survival, disease-free survival (DFS), and nonrelapse mortality (NRM) for patients with high-risk disease or those given bone marrow as a graft source. However, for patients with intermediate-risk disease receiving peripheral blood grafts, we observed higher NRM and lower overall survival (OS) in the 10/10 MUD group compared to the MSD cohort. Graft-versus-host disease (GVHD) was higher in the MUD group compared to the MSD group. These results suggest that if a patient has high-risk disease and an MSD is not available, selection of an HLA-allele-matched MUD may provide similar OS and DFS, and therefore lack of an MSD in and of itself should not preclude such a patient from undergoing transplantation. However, for patients with intermediate-risk disease, transplantation with peripheral blood from a 10/10 MUD is associated with lower survival than an MSD.