Hemorrhagic cystitis (HC) remains a common complication of allogeneic blood and marrow transplantation. Previous analyses of risk factors for this complication were performed in heterogenous populations, with dissimilar diagnosis and conditioning regimens. We postulated that HC is more prevalent in matched unrelated donor (MUD) and unrelated cord blood (UCB) transplantations than in matched related donor (MRD) transplantations. We performed a retrospective study on 105 acute lymphocytic leukemia patients treated with 12 Gy total body irradiation-based regimens and allogeneic transplants (MUD, n = 38; UCB, n = 15; mismatched related, n = 20; MRD, n = 32). HC occurred in 16% of patients receiving MRD transplants, 30% of recipients of mismatched related, and 40% of MUD or UCB transplants (hazard ratio 2.9, 95% CI 1.0-7.9 for the comparison of MRD versus MUD). The excessive rate of HC among MUD and UCB patients became evident after the first 30 days after transplantation. Recipients younger than 26 years had a significantly higher incidence of HC (HR 2.5, 95% CI 1.1-5.8). This donor type and age effect was independent of platelet engraftment, development of graft-versus-host disease (GVHD), source of stem cells, use of anti-thymocyte globulin (ATG) or cyclophosphamide in the regimen, steroid use, or stem cell source. We concluded that HC is more prevalent in MUD and UCB transplantations. © 2004 by The American Society of Hematology.