The outcome of unrelated donor bone marrow transplantation for aplastic anemia is inferior to that of sibling donor bone marrow transplantation because of a higher rate of transplant-related mortality (TRM), which is closely associated with the intensity of pretransplant conditioning to overcome graft rejection. We conducted a prospective trial with an intermediate to high dose of total body irradiation (TBI) in combination with a fixed dose of cyclophosphamide (120 mg/kg) to use for pretransplant conditioning for unrelated donor bone marrow transplantation in adult aplastic anemia. The number of patients who received doses of 1200, 1000, and 800 cGy of TBI were 5, 9, and 26, respectively. The corresponding probabilities of overall survival (OS) at 3 years were 40%, 44%, and 92%, respectively. The incidence of regimen-related toxicity with grade III-IV and graft rejection in the patients who received a dose of 800 cGy of TBI were 0 of 26 patients. The significant factors associated with OS were the TBI dose (800 cGy vs. >or=1000 cGy; P = .001), chronic graft-versus-host disease (less than or equal to limited vs. extensive; P = .013), the method of HLA typing for the donor-recipient matching (serologic typing vs. DNA-based typing; P = .006), and the transfusion amount before transplantation (<or=90 vs. >90 units; P = .020).