Effects of race or ethnicity on survival after high-dose chemoradiation followed by stem cell transplantation (SCT) have not been thoroughly evaluated. We analyzed survival according to racial/ethnic categories for 3587 consecutive patients who had SCT at a single US institution between July 1992 and December 2000. Among 1366 patients who received autologous SCT, race or ethnicity was not significantly associated with survival. In contrast, among 2221 patients who received allogeneic SCT from HLA-matched unrelated or sibling donors, blacks had a significantly greater mortality than whites (unadjusted hazard ratio, 1.65; 95% confidence interval, 1.21-2.25). Mortality among other racial or ethnic groups was not significantly different from that among whites. The greater mortality hazard among blacks persisted after controlling for donor type, pretransplantation risk category, patient age, donor/patient sex, and cytomegalovirus exposure (hazard ratio, 1.71; 95% confidence interval, 1.25-2.34). SCT from both HLA-matched unrelated and HLA-identical sibling donors was associated with more severe acute graft-versus-host disease and higher nonrelapse mortality among blacks compared with whites. Furthermore, blacks who received SCT for chronic myeloid leukemia had longer diagnosis-to-transplantation intervals than whites. A matched-cohort analysis showed that the higher mortality among blacks could not be explained by obvious socioeconomic differences. The higher incidence of severe graft-versus-host disease among blacks compared with whites, both with HLA-identical sibling donors, might be related to yet-unidentified "immune-enhancing" genetic polymorphisms. We cannot exclude the possibility that the increased mortality risk among blacks after discharge from the transplant center might in part be related to unidentified sociocultural differences that influence medical care.