Persistence of disease after salvage therapy among relapsed or refractory Hodgkin lymphoma (HL) patients predicts poor outcome. Here, we report on 41 HL patients with active disease after salvage therapy and who received high-dose melphalan (HD-PAM) and auto-SCT as a bridge to a second autologous or an allogeneic transplantation between 2002 and 2013 at our center. Disease response was based on 18-fluoro-deoxyglucose-positron emission tomography results in all patients. Overall response rate after HD-PAM was 78% and it did not differ among PR or stable/progressive disease patients (P=1.00). Response was associated with better OS: hazard ratio=0.32 (95% confidence interval: 0.13-0.77, P=0.01) irrespective of disease status before HD-PAM. Thirty-three patients (80%) were able to complete the planned treatment, intended as tandem autologous or auto-allo transplant. Hematological and extrahematological toxicity of HD-PAM was manageable, without any treatment-related death. In conclusion, HD-PAM is a valuable therapeutic option in relapsed/refractory HL patients with active disease after salvage therapy, with an impressive 78% overall response rate and 80% rate of proceeding to further transplantation. The present data may be integrated with the growing literature on new drugs in the field of relapsed/refractory HL.