Aplastic anemia (AA) is a rare hematopoietic stem cell disease, which can be treated with horse antilymphocyte globulin (ALG) for patients not eligible for bone marrow transplantation. ALG gives about 60% overall survival rate (OS) after 5 years, a 30% of persistent complete remission and a 20% early death rate related to failure. ALG has been incriminated in the emergence of 10 to 20% therapy-related AML/MDS (t-AML/MDS) with the usual doses. Questions remain whether higher doses of ALG could improve the response and OS rates and whether the combination with androgens is able to protect patients from t-AML/MDS. We have carried out a single institutional retrospective study of 87 AA treated with higher doses of ALG, twice the usual posology (140 mg/kg instead of 75 mg/kg), combined to androgens. The overall response rate was 77% and the OS rate at 5 years was 78%. Androgens in combination with ALG improved response and OS rates. At diagnosis, 6% of AA had an abnormal karyotype using conventional cytogenetic not related to any time-to-event. Two patients displayed a cytogenetic conversion related to the occurrence of secondary malignancies. The incidence of t-AML/MDS was 2.3% with an estimated 10-year cumulative incidence of 3.1. Our results show that higher doses of ALG combined to androgens are feasible and give results close to those recently describe with the immunosuppressive treatments including ALG associated to cyclosporine, with a low SMD/AML incidence rate.