While survival outcomes have significantly improved, up to 40% of patients die within 1-year after HLA-matched unrelated donor (URD) blood and marrow transplant (BMT). To identify non-HLA genetic contributors to mortality after BMT, we performed the first exome-wide association study in the DISCOVeRY-BMT cohorts using the Illumina HumanExome BeadChip. This study includes 2,473 AML, ALL, MDS patients and 2,221 10/10 HLA matched donors treated from 2000-2011. Single variant and gene-level analyses were performed with overall survival (OS), transplant-related mortality (TRM), and disease-related mortality (DRM). Genotype mismatches between recipients and donors in a rare nonsynonymous variant of a testis expressed gene TEX38 significantly increased risk of TRM, which was more dramatic when either the recipient or donor was female. Using SKAT-O test to evaluate gene-level effects, variant genotypes of OR51D1 in recipients were significantly associated with OS and TRM. In donors, four (ALPP, EMID1, SLC44A5, LRP1), one (HHAT), and two (LYZL4, NT5E) genes were significantly associated with OS, TRM, and DRM, respectively. Inspection of NT5E crystal structures shows four of the associated variants impact the enzyme structure and likely decrease the enzyme’s catalytic efficiency. Further confirmation of these findings and additional functional studies may provide individualized risk prediction and prognosis, as well as alternative donor selection strategies.