The prognosis of adult patients with relapsed acute lymphoblastic leukemia (ALL) remains poor. Recent studies in adolescents and young adults reported better outcomes when therapy was intensified. Based on hyper-CVAD (cyclophosphamide/vincristine/doxorubicin/dexamethasone) as a backbone, we designed an augmented version with intensified doses of vincristine, dexamethasone, and asparaginase (L-asparaginase in the first 62 patients and pegaspargase in the remainder) starting from course 1. Ninety patients have been enrolled, with a median age of 34 years (range, 14-70 years). Most patients (78%) had pre-B ALL and were in first salvage (76%), with a first remission duration of 12.6 months (range, 1-78 months). Ten patients had primary refractory disease. Of 88 evaluable patients, 41 (47%) achieved complete remission (CR), with a median time to CR of 29 days (range, 18-80 days). Eight patients (9%) died within the first 30 days. Median CR duration, progression-free survival, and overall survival were 5, 6.2, and 6 months, respectively. Median overall survival of CR patients was 10.2 months (range, 1.4-69.5+ months). Twenty-eight patients (32%) proceeded to stem cell transplantation. Myelosuppression-associated complications were frequent. Pegaspargase was equally effective and easier to administer than L-asparaginase. Augmented hyper-CVAD may be suitable to be studied in younger adults with untreated ALL.