Allogeneic hematopoietic SCT (HSCT) is currently the only curative treatment for myelodysplastic syndrome (MDS). However, many patients cannot find an HLA-matched donor. We have developed a new protocol for HLA-mismatched (including haploidentical) HSCT using G-CSF-primed BM plus G-CSF-mobilized PBSCs without in vitro T-cell depletion. A total of 36 patients diagnosed with high-risk MDS (RAEB (refractory anemia with excess blasts) or RAEBt (RAEB in transformation)) underwent transplantation from HLA-mismatched family donors. All patients achieved sustained myeloid engraftment. The cumulative incidence of grades II-IV acute GVHD (aGVHD) was 60% and that of grades III and IV aGVHD was 15%. The 2-year cumulative incidence of chronic GVHD was 56%. After a median follow-up of 17 months, 4 patients had relapsed and died and 25 patients were still alive. The 2-year probability of leukemia-free survival (LFS) was 65%. Patients transplanted within 7 months of diagnosis had better LFS (89 vs 43% ). Severe aGVHD decreased the LFS significantly by increasing non-relapse mortality (NRM). This study confirms that HLA-mismatched HSCT is a treatment option for MDS. Patients with high-risk MDS benefit from receiving HSCT early in the course of the disease.