Background and Objectives: In adult acute lymphoblastic leukaemia (ALL), unlike in childhood ALL, the percentage of long-term remitters and survivors has not improved significantly over the last decades. In the present analysis, we describe a series of adult ALL patients consecutively treated with the same regimen in order to analyse prognostic factors and treatment outcome as well as to define new risk-oriented strategies. Design and Methods: From 1990 to 1998, 102 newly diagnosed ALL patients were referred to our division, 83 of them were eligible for the present study. Median age was 31 years (range 13–76); 77.1% had B-lineage ALL and 22.9% T-lineage ALL; 36.1% showed associated myeloid markers. All patients received an induction phase treatment, consisting of a 4-week cycle with vincristine, daunorubicin, L-asparaginase and desametasone; the consolidation phase included cyclophosphamide, cytarabine, 6-mercaptopurine and central nervous system (CNS) prophylaxis, followed by three of months maintenance (methotrexate + 6-mercaptopurine), re-induction (4-week cycle with vincristine, adriamicin, desametasone), and 2-year maintenance with methotrexate + 6-mercaptopurine. Results: Complete remission (CR) was achieved in 66 patients (79.5%); 20.5% of patients were resistant. The relapse rate was 60.2%. There were 10 CNS relapses (accounting for 12% of all patients, 15% of all CRs and 20% of all relapses). One patient had an ovarian and 2 had a breast relapse. Eleven patients remained in first continuous CR after chemotherapy. Median overall survival (OS) and disease-free survival (DFS) were 1.8 and 1.0 years, respectively, with a median follow-up of 5.6 years (range 0.3–12.1). Initial white blood cell count ≤30 × 109/l, age <35 years, and time to complete remission ≤40 days were the most significant prognostic factors for OS (p < 0.05). These three characteristics defined a group of patients with a better prognosis (5-year OS: 58%). They represented, however, only 18% in this series of adult patients. Interpretation and Conclusions: In our cohort, we were able to define a small subgroup of adult ALL patients with a better outcome. However, the majority of patients is at a high risk of failure when treated with standard protocols. There is a need for new, more active regimens for these patients.