This study evaluates the prognostic value of minimal residual disease (MRD) monitoring by multiparametric flow cytometry in 41 patients with acute myeloid leukemia or myelodysplastic syndrome undergoing allogeneic transplantation. MRD assessment after transplant (day +100) allowed to discriminate different risk populations, being the most significant cut-off value for outcome level of MRD </≥10−3. Outcome was significantly better among patients with low (<10−3) versus high (≥10−3) MRD at day +100 after transplant. Thus, overall survival was 73% versus 25% at 4 years among patients with low versus high MRD at day +100 after transplant (P = 0.002); 74% of patients with low MRD were event free at 4 years as compared to 17% among patients with high MRD (P = 0.01). In multivariate analysis, MRD value as well as chronic GVHD significantly influenced outcome. In conclusion, MRD monitoring early post-transplant is an important tool for outcome prediction and should be considered in decision making after allogeneic transplantation. Am. J. Hematol. 2009. © 2008 Wiley-Liss, Inc.