Purpose : To evaluate the use of reduced-intensity (RI) conditioning with allogeneic hematopoietic stem cell transplantation (HSCT) from HLA-identical family donors in patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). Patients and Methods: Sixteen patients (median age, 54 years; range, 37 to 66 years) underwent RI-HSCT using a conditioning regimen of fludarabine 25 mg/m(2) daily for 5 days and either cyclophosphamide 1 g/m(2) daily for 2 days (14 patients) or melphalan 140 mg/m2 for 1 day (two patients). The median number of CD34(+) cells and CD3(+) cells infused per kilogram of recipient weight was 4.5 x 10(6) (range, 1.8 to 7.3 x 10(6) cells) and 2.9 x 10(8) (range, 0.1 to 9.6 x 10(8) cells), respectively. Results: There was no transplant-related mortality (TRM) within 100 days of HSCT. Grade 1 to 2 acute graft-versus-host disease (GVHD) occurred in three patients, but neither grade 3 nor grade 4 disease was observed. Chronic GVHD occurred in 10 patients. One patient had cytomegalovirus (CMV) reactivation but did not develop CMV disease. With a median follow-up of 26 months (range, 15 to 45 months), 11 patients are alive (nine in continuous complete remission and one in complete remission after a second transplantation), and five have died (four from disease progression and one from bone-marrow aplasia induced by cyclosporine withdrawal). The 2-year actuarial overall and event-free survival rates were 69% (95% confidence interval [Cl], 40% to 86%) and 56% (95% Cl, 30% to 68%), respectively. Conclusion: This strategy of RI-HSCT resulted in reliable engraftment with low incidence of acute GVHD and TRM. Durable remissions were observed in patients with MDS and AML consistent with a graft-versus-leukemia effect.