Several single-institution pilot studies have suggested that augmented preparative regimens, including those containing total body irradiation combined with an autologous bone marrow transplantation, are superior to standard regimens for the treatment of relapsed or refractory Hodgkin disease. On the basis of these data, we undertook, in the cooperative group setting, a phase II trial of augmented preparative regimens for patients experiencing treatment failure with conventional chemotherapy. Eighty-one patients with either sensitive or refractory (induction failures or chemoresistant) relapse received etoposide (60 mg/kg), cyclophosphamide (100 mg/kg), and either total body irradiation (12 Gy) or, if previously irradiated, carmustine (15 mg/kg), followed by an autologous bone marrow transplantation. Progression-free (PFS) and overall (OS) survival were estimated, and a Cox regression model was used to assess potential prognostic variables. The 5-year PFS and OS for the 74 eligible patients treated at 20 Southwest Oncology Group centers were 41% (95% confidence interval [CI], 29%-53%) and 54% (95% CI, 43%-65%), respectively, despite a median remission after initial chemotherapy of only 6 months. The 3-year OS for those whose induction therapy failed was 72% (95% CI, 52%-93%). There was 1 (1.4%) early treatment-related death, 2 late deaths due to lung toxicity, and only 1 death due to myelodysplasia. There were no differences in PFS or OS on the basis of regimen or chemosensitivity. A Cox prognostic factor analysis determined that >2 prior regimens, relapse in a radiated field, and extranodal disease were adverse prognostic factors. Among the 46 patients who received prior radiotherapy, the 5-year OS was 38% (95% CI, 14%-61%) for patients with 2 or 3 adverse factors, versus 60% (95% CI, 42%-78%) for those with 0 factors or 1 adverse factor. Augmented preparative regimens seem promising for the treatment of relapsed or refractory Hodgkin disease, without an increase in regimen-related mortality. A poor-prognosis group was identified that should be treated with novel therapies.