Abstract In this monocentric prospective study, the influence on long‐term outcomes of peripheral blood levels of monocytic‐myeloid‐derived suppressive cells (M‐MDSC) was investigated in 56 patients with acute leukemia (myeloid n = 47; lymphoid n = 9) before and after (Days+60/+90) allogeneic hematopoietic stem cell transplantation (Allo‐HSCT). A risk of relapse was found to be associated with a level of pregraft M‐MDSC above 1.4% by ROC curve analysis. In multivariate analysis, this threshold retained a strong statistical significance (HR: 5.94 [2.09–16.87], p = 0.001). Considering only the group of patients who were in complete remission prior to Allo‐HSCT (n = 44), a significant prediction of relapse was found to be associated, in multivariate analysis, with a level of pregraft M‐MDSC above 1.4% (HR: 55.01 [14.95–202.37], p