Mantle-cell lymphoma (MCL) is characterized by poor prognosis with a median survival of only 3 to 4 years. To improve clinical outcome, the European MCL Network initiated a randomized trial comparing consolidation with myeloablative radiochemotherapy followed by autologous stem cell transplantation (ASCT) to alpha-interferon maintenance (IFN alpha) in first remission. Patients 65 years of age or younger with advanced-stage MCL were assigned to ASCT or IFN alpha after achievement of complete or partial remission by a cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)-like induction therapy. According to the International Prognostic Index (IPI), 43% of patients had a low-risk, 41% a low-intermediate, 11% a high-intermediate, and 6% a high-risk profile. Sixty-two of 122 patients proceeded to ASCT and 60 received IFN alpha. Patients in the ASCT arm experienced a significantly longer progression-free survival (PFS) with a median of 39 months compared with 17 months for patients in the IFN alpha arm (P = .0108). The 3-year overall survival (OS) was 83% after ASCT versus 77% in the IFN group (P = .18). Early consolidation by myeloablative radiochemotherapy followed by ASCT is feasible and results in a significant prolongation of PFS in advanced-stage MCL. Longer follow-up is needed to determine the effect on OS.