Thalidomide has become one of the standard treatments of multiple myeloma patients either at diagnosis or in relapse and refractory disease. Up to date there are no randomized trials comparing the efficacy of thalidomide to other chemotherapy combinations in relapsed and refractory disease. We have conducted a retrospective analysis comparing the outcome of patients (n=141) younger than 65 years old who received either thalidomide (Group A; n=58) or non-thalidomide containing regimens including dexamethasone, cylophosphamide, melphalan+ prednisone, VAD (Group B; n=83) at first or second relapse post autologous stem cell transplant. The two groups were comparable in respect to age at relapse, Durie Salmon staging, IPS staging, serum beta-2 microglobulin, serum albumin and ECOG performance status. The median time to relapse from the date of initiation of salvage therapy in the thalidomide group was 12.1 months vs 6.5 months in the non-thalidomide group (p < 0.05). The median overall survival from the time of diagnosis was significantly longer in the thalidomide group (median survival = 131 months) vs the non-thalidomide group (median survival 50 months) (p =0.0055) (Figure below). In summary our retrospective analysis supports the superiority of thalidomide in the treatment of younger relapsed and refractory myeloma patients when compared to other previously established salvage chemotherapy regimen.