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Currently, there is no well-accepted rating system for reliably predicting which HLA-mismatched (MM) unrelated donor should be selected for a patient without an HLA allele-matched donor. We evaluated the ability of an MM ranking system, HistoCheck, to predict the risk associated with HLA class I disparity in a population of 744 single allele or antigen HLA-A, -B, or -C MM myeloablative unrelated donor hematopoietic stem cell transplantation recipients with acute myelogenous leukemia, acute lymphoblastic leukemia, chronic myelogenous leukemia, or myelodysplastic syndrome, facilitated through the National Marrow Donor Program between 1988 and 2003. Multivariate models were used to adjust for other significant clinical risk factors. HLA MMs were scored using the HistoCheck Web-based tool, and the patients were divided into 4 quartiles: dissimilarity score (DSS) 1.04-2.84 (allele MM), DSS >2.84-13.75 (allele and antigen MM), DSS >13.75-19.39 (antigen MM), and DSS >19.39-36.62 (antigen MM). Using the lowest scoring quartile as the reference, the DSS groups were evaluated for associations with relapse, treatment-related mortality, acute and chronic graft-versus-host disease, leukemia-free survival, and overall survival in the entire cohort and also in subset analyses by disease and disease stage. No significant associations were found between DSS and any outcomes in the overall cohort using the quartile categories or treating DSS as a continuous variable. Higher DSS scores were associated with decreased engraftment in early-stage disease (P = .0003), but not in other disease stages. In summary, DSS does not correlate with transplantation outcomes, and the HistoCheck scoring system does not provide an effective technique for ranking HLA class I MM. The dataset used in this study is available to evaluate new algorithms proposed for donor selection. [Copyright &y& Elsevier]