This study explored the effect of thalidomide and cyclophosphamide on stem cell collection, in addition to assessing their efficacy as induction therapy for myeloma patients destined for autologous stem cell transplantation (ASCT). We analyzed newly diagnosed myeloma patients who received TCD (thalidomide 100 mg/day for 28 days, oral cyclophosphamide 150 mg/m2/day and dexamethasone 40 mg/day on days 1-4) as induction therapy prior to ASCT. Peripheral stem cells were mobilized with granulocyte colony-stimulating factor and cyclophosphamide. Thirty-six patients (median age 54 years) received TCD chemotherapy (median 4 cycles). The overall response rate to TCD was 77.8% (28/36). The median number of CD34+ cells was 6.5 × 106/kg, and 2 patients failed to achieve the optimal number of CD34+ cells, i.e. 4.0 × 106/kg, although they were able to attain >2.0 × 106/kg. The overall response rate increased up to 94.4% (34/36) after ASCT; this included 9 patients with a stringent complete response without transplantation-related mortality. Four patients died due to disease progression and 17 were found to have progressed after ASCT (the median progression-free survival after ASCT was 19.6 months). TCD chemotherapy can be an effective and feasible induction regimen prior to ASCT for myeloma patients.