BACKGROUND: Double‐cord‐blood transplantation (DCBT) offers an option for patients receiving reduced‐intensity transplants. These unique transplants have two donors, both of whom are usually HLA mismatched at one to two loci.STUDY DESIGN AND METHODS: Fifty‐three patients were recipients of a reduced‐intensity DCBT. Cords were at least 4/6 allele‐level HLA‐A, ‐B, and ‐DR match with the patient and each other with a minimum combined cell dose of more than 3.7 × 107 total nucleated cells per kg. Twenty‐one patients received cyclosporine/mycophenolate mofetil and 32 patients received sirolimus/tacrolimus (SIR/TAC) for graft‐versus‐host disease prophylaxis. The effect of allele level HLA typing on clinical endpoints of overall survival (OS), disease‐free survival (DFS), engraftment, and acute graft‐versus‐host disease (aGVHD) were assessed.RESULTS: Neutrophil (p = 0.001) engraftment and platelet engraftment (p = 0.027) were significantly faster in patients who have closer Class I (HLA‐A, ‐B, ‐C) matching. Neutrophil engraftment was faster in patients who had closer HLA‐B matching to their combined cords (p = 0.007). There was a low incidence of aGVHD overall, especially in the SIR/TAC group. Class I HLA matching had no effect on aGVHD. HLA‐DR and ‐DQ had no effect on engraftment or aGVHD.CONCLUSION: Class I allele matching, and HLA‐B matching specifically, were associated with faster neutrophil engraftment. High‐resolution HLA matching did not affect OS or DFS.