Peripheral T-cell lymphomas (PTCL) show a poor outcome following conventional chemotherapy. However, the role of high-dose therapy is still unclear. We initiated a prospective multicenter phase II study to evaluate the feasibility and the efficacy of myeloablative radiochemotherapy followed by autologous peripheral blood stem cell transplantation (APBSCT) as first-line treatment in PTCL. After 4-6 courses CHOP (cyclophosphamide, doxorubicine, vincristine, and prednisone) chemotherapy, an induction therapy with either the DexaBEAM (dexamethasone, carmustine, melphalan, etoposide, and cytarabine) or the ESHAP (etoposide, methylprednisolone, cytarabine, and cisplatin) protocol was administered. If a complete (CR) or a partial remission (PR) was achieved, myeloablative radiochemotherapy (hyperfractionated total body irradiation and high-dose cyclophosphamide) with APBSCT was performed. From June 2000 to November 2002, 30 patients (pts) were enrolled into the study. The two main PTCL subgroups included were PTCL not specified and angioimmunoblastic T-cell lymphoma (each n=12). In all, 21 of the 30 pts (70%) were transplanted. The main toxicities were myelosuppression and infections. The overall response rate after myeloablative therapy was 100% (20 CR, one PR). In total, 16 of 21 transplanted pts (76%) remained in CR at a median follow-up of 15 months (range, 6-32 months) from treatment start. Nine pts received no APBSCT mainly due to progressive disease. In conclusion, this first prospective PTCL-restricted study of frontline myeloablative radiochemotherapy with APBSCT shows feasibility and high efficacy. Our data suggest a substantial impact on outcome, however, longer follow-up is necessary to confirm survival benefit.