In order to assess the mortality and toxicity of the Hyper-CVAD protocol used as first-line treatment of acute lymphoblastic leukemia, a retrospective cohort study was performed in patients less than 40 years of age from March to September 2011 treated with Hyper-CVAD regimen. Mortality and toxicity was compared with the results of patients treated with the institutional HGMLAL07 regimen between 2009-2012. 18 patients were included; the median age was 26 years old. Complete remissions (67.7% versus 81.9%) as well as one-year (40% versus 62%) and 2 year survival rates (18% versus 34%) were lower with the Hyper-CVAD regimen. By selecting only patients younger than 35 years, the effectiveness of Hyper-CVAD was also lower. In our experience and because of its high cost and toxicity, the Hyper-CVAD regimen should be limited to patients with relapsed or refractory leukemia.