BACKGROUND: Double autologous stem cell transplantation (ASCT) seems to be superior to a single ASCT, at least in the patients who did not achieve a 90% response after the first transplant. An allogeneic SCT with a dose-reduced conditioning regimen after ASCT and as part of the initial therapy, might be a feasible and highly effective approach. The aim of this study was to determine the prognostic factors that are associated with the outcome of multiple myeloma (MM) patients who had received a second transplant. METHODS: From April 1996 to December 2004, 38 MM patients, who had previously received high-dose melphalan (200 mg/m2) with autologous stem cell support, underwent a second transplant. Following the 1(st) ASCT, 24 patients received a second ASCT and 14 received a tandem reduced-intensity conditioning allogeneic stem cell transplantation (RIST) from their HLA-matched siblings. RESULTS: The 3-year estimated PFS and overall survival (OS) from the time of the first ASCT were 25.2% and 77.6%, respectively. The median PFS and OS were 26 months (95% CI, 23~29) and 60 months (95% CI, 44~76), respectively. The disease status (a CR vs. PR or less) at the second transplant was be the most powerful factor for improving the PFS (P=0.001, hazard ratio 5.8, 95% CI 2.1~16.1). CONCLUSION: Patients whose disease is sensitive to chemotherapy and who obtain a CR after a single transplantation might benefit the most from a second transplant.