Conventional chemotherapy has failed to substantially prolong survival for patients with advanced follicular lymphoma. To improve outcomes, the German Low-Grade Lymphoma Study Group (GLSG) initiated a randomized trial to compare the effect of potentially curative myeloablative radiochemotherapy followed by autologous stem cell transplantation (ASCT) with interferon-alpha (IFN-alpha) maintenance therapy in first remission. Three hundred seven patients (younger than 60 years) with follicular lymphoma were recruited into the trial from 130 institutions. After 2 cycles of cyclophosphamide-doxorubicin-vincristine-prednisone (CHOP) or mitoxantrone-chlorambucil-prednisone (MCP) induction chemotherapy, patients were randomly assigned to either the ASCT or the IFN-alpha group. The respective therapy was started when patients achieved complete or partial remission after induction chemotherapy. Two hundred forty patients with follicular lymphoma are evaluable for the comparison of ASCT and IFN-alpha. In patients who underwent ASCT, the 5-year progression-free survival (PFS) rate was 64.7%, and in the IFN-alpha arm it was 33.3% (P < .0001). As expected, acute toxicity was higher in the ASCT group, but early mortality was below 2.5% in both study arms. In this randomized, multicenter trial, high-dose radiochemotherapy followed by ASCT significantly improved PFS compared with IFN-alpha in patients with follicular lymphoma when applied as consolidation in first remission. Longer follow-up is necessary to determine the effect of ASCT on overall survival.