Hematopoietic cell transplantation is the only curative therapy for patients with myelodysplastic syndrome (MDS). However, treatment-related toxicity and, in patients with advanced MDS (refractory anemia with excess blasts [RAEB]; RAEB in transformation [RAEB-T]) or transformation to acute myeloid leukemia with multilineage dysplasia (tAML), posttransplantation relapse continue to be prevalent. Induction chemotherapy (IC) has been used in an attempt to decrease the risk of posttransplantation relapse, but the benefit for posttransplantation long-term survival is uncertain. We reviewed results in 125 patients with advanced MDS and tAML who received transplants from HLA-identical related or unrelated donors after preparation with myeloablative conditioning regimens. Thirty-three patients (3 with RAEB, 6 with RAEB-T, and 24 with tAML) received IC before transplantation, and 92 patients (62 with RAEB, 22 with RAEB-T, and 8 with tAML) did not. Seventy-six patients were conditioned with oral busulfan 16 mg/kg, which was adjusted to achieve steady-state plasma concentrations of 800 to 900 ng/mL, plus cyclophosphamide 2 x 60 mg/kg, and 49 patients received busulfan 7 mg/kg (without dose adjustment) and total body irradiation 6 x 200 cGy given over 3 days. There was no evidence of a benefit in posttransplantation outcome associated with prior IC, either for patients with RAEB/RAEB-T or those with tAML, with either conditioning regimen. There was a correlation of the severity of pretransplantation flow cytometric aberrancies on marrow cells and posttransplantation relapse. Further studies that randomize patients to IC versus no IC need to appropriately address the possible beneficial effect of IC.