Mixed phenotype acute leukemias are infrequent and considered high risk. The optimal treatment approach and the role of allogeneic hematopoietic stem cell transplantation are not entirely clear. In this study, we investigated 519 patients with mixed phenotype acute leukemia in first complete remission who underwent allogeneic hematopoietic stem cell transplantation between 2000 and 2014, and who were reported to the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation (EBMT). Median age was 38.1 years (range 18-75). Cytogenetics classified 49.3% as poor risk. At three years, relapse incidence was 31.4% (26.9-35.9), non-relapse mortality was 22.1% (18.4-26.1), the leukemia-free survival was 46.5% (41.7-51.4), and the overall survival was 56.3% (51.5-61.2). At six months, 32.5% had developed acute graft-versus-host disease, while at three years, 37.5% had developed chronic graft-versus-host disease (32.6-42.3). In a multivariate analysis, age and year of transplant had a strong impact on outcome. Myeloablative conditioning using total body irradiation correlated with a better leukemia-free survival. Our study suggests that mixed phenotype acute leukemia is potentially sensitive to graft-versus-leukemia and thus can benefit from allogeneic hematopoietic stem cell transplantation with a potential for cure.