We prospectively compared two strategies of allogeneic PBSCT from HLA-identical siblings in adults with poor-risk AML or myelodysplastic syndrome with >5% marrow blasts in an early disease status (AML or refractory anemia with excess blasts (RAEB type 2) in first remission after chemotherapy or untreated RAEB type 1). Based only on age, all consecutive patients were offered one of two specific transplant protocols. Patients ≤50 years old received conventional high-dose conditioning with cyclophosphamide-TBI and use of CD34+-selected PBSCT (CTCD34+ group), while patients aged >50 years received a reduced-intensity conditioning (RIC) with fludarabine and oral busulphan (FB-RIC). Seventy-five patients entered the study (35 in the CTCD34+ and 39 in the FB-RIC group). The median follow-up was >4 years in both groups. The 4-year non-relapse mortality (NRM) was 19 and 20%, respectively (P = 0.8). Relapse and survival were also equivalent in both groups. These results suggest that in this setting, the expected high NRM in elderly patients can be reduced with an RIC regimen.