We evaluated with an intent-to-treat analysis the response rate, the disease-free survival (DFS), and the overall survival after a multidrug salvage regimen (VIM3ARAC), followed by stem-cell transplantation (SCT) in case of response, in patients with aggressive non-Hodgkin's lymphoma (NHL) who progressed on or after the first-line therapy. Seventy-one patients (refractory: 15; relapse 'on therapy': 36; and relapse 'off therapy': 20) received two courses of VIM3ARAC (teniposide, ifosfamide, mitoxantrone, mitoguazone, high-dose methotrexate, high-dose cytarabine, prednisolone). SCT was performed only in patients with minimal disease after the second course. The response rate was 72%. It was not influenced by response to first-line therapy. Forty-eight patients (68%), including 32 complete responders, fulfilled response criteria for SCT. Thirty-six patients underwent SCT (allogeneic: 3; autologous: 33). The 4-year DFS rate of the 48 responding patients was 39%. The actuarial survival at 4 years was 34% for all patients. Relapse off therapy and a performance status <2 at relapse were the only two independent favorable prognostic factors for survival. In conclusion, VIM3AraC is associated with a high response rate in relapsing and refractory aggressive NHL. Up to half of the patients could receive SCT. This chemotherapy, followed by SCT could durably salvage 34% of these patients.