Background and Aim: Acute lymphoblastic leukemia (ALL) is a malignant disorder with the origin of B or T lymphocyte progenitor. This malignancy presents with anemia, thrombocytopenia and neutropenia due to suppression of hematopoiesis by increasing blast cells in bone marrow. With regard to many reports on effectiveness of HyperCVAD regimen in ALL patients and inadequate data from Iranian patients, the present study was conducted to assess the efficacy of this regimen in Iranian patients. Materials and Methods: This comparative before-after study included 36 adults with newly diagnosed ALL referred to Taleghani hospital between September 2004 and September 2007. Treatment consisted of four cycles of HyperCVAD alternating with four cycles of high dose methotrexate (MTX) and cytarabine with intrathecal prophylaxis and supportive care with antibiotic prophylaxis and G-CSF. Maintenance included 2 years of treatment with mercaptopurine, MTX, vincristine and prednisolone. Results of treatment on complete remission and survival were evaluated. Results: Mean age of patients was 21±11.3 years. Mature B-cell disease (Burkitt-type) was present in 2.7%, T-cell disease in 25%, and leukocytosis of more than 30×109/L, Philadelphia chromosome, and mediastinal mass were found in 27.8%, 8%, and 8% of patients, respectively. The complete response and mortality during induction were 91.6% and 2.7%, respectively, while estimated median survival time and estimated median CR duration were 13 and 8.3 months, respectively. Conclusion: Our results revealed that efficacy of HyperCVAD regimen in our patients were inferior to other studies. We recommend another study with larger sample size to compare the efficacy of this regimen with other standard regimens.