We analyzed outcomes of patients with myelodysplastic syndrome (MDS) or secondary acute myelogenous leukemia (sAML) that were treated at our institution with a reduced intensity conditioning (RIC) regimen of 550-cGy total body irradiation and cyclophosphamide followed by related donor (RD) or unrelated donor (URD) transplantation. Fifty-one consecutive patients with MDS or sAML received this RIC regimen and URD (n = 30) or RD (n = 21) stem cells. Graft-versus-host disease prophylaxis consisted of cyclosporine alone (RD) or with corticosteroids and methotrexate (URD). Median patient age was 44 years. With a median follow-up of 3.7 years after transplantation in the 19 surviving patients (37%), Kaplan-Meier estimates of overall survival were 88%, 46%, 33%, and 11% for patients transplanted with sAML in remission, refractory anemia, refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, or sAML refractory/untreated, respectively. Kaplan-Meier estimates of relapse-free survival were 75%, 46%, 33%, and 11%, respectively. Overall, the cumulative incidences of relapse and transplant-related mortality were 27% and 37%, respectively. In patients with MDS, this is an effective RIC regimen for allogeneic transplantation that can be used as an alternative to other RIC or conventional conditioning regimens.