Several high-dose therapy regimens are used for autologous hematopoietic stem cell transplantation (auto-HSCT) for relapsed and refractory Hodgkin's lymphoma (HL) with variable disease response. An intensified regimen of etoposide (VP-16) 2400 mg/m(2), cyclophosphamide 7200 mg/m(2) and carmustine ( BCNU) 600 mg/m(2) (VCB) pre-auto-HSCT was developed to overcome disease recurrence. A total of 43 relapsed and refractory HL patients underwent auto-HSCT between January 1992 and December 2004. At day 100 there were 37 (86%) complete responses. A total of 40 patients survived beyond day 100,14 of whom subsequently relapsed/progressed. At a median follow-up of 4.9 years (range 1.5-11.4 years), 26 patients (60%) are alive and disease free. Five-year actuarial event-free survival (EFS) was 53% (95% CI 35-70%) and median EFS was 5.9 years. Median progression-free and overall survival shave not been reached. EFS was reduced with an increasing number of prognostic factors (Karnofsky performance status, KPS < 90, chemo therapy-resistant disease and >= 3 chemotherapy regimens prior to transplant <= 1 vs >= 2; P = 0.049). Grade III-IV regimen-related toxicity was 9% (n = 4). The 1-year cumulative incidence of interstitial pneumonitis (IP) was 36%, however only two patients died of IP complications. Disease progression was the most common cause of death (n = 10,23%). Intensive VCB is an effective and well-tolerated preparative regimen for relapsed and refractory HL auto-HSCT.