This randomized, retrospective study evaluated the effect of thalidomide combined with bortezomib-dexamethasone (TBD) or vincristine-doxorubicin-dexamethasone (T-VAD) on 46 patients with multiple myeloma. Newly diagnosed patients were randomly allocated to receive TBD (n = 24) or T-VAD (n = 22). The high-quality response rate (complete response plus very good partial response) was 62.5% in the TBD group and 45.4% for T-VAD. The complete response rate was 29.2% for TBD and 13.6% for T-VAD. Overall survival at 2 and 3 years, respectively, was 91.7% and 62.5% for TBD versus 86.4% and 54.5% for T-VAD. Most of the toxic effects of treatment were well tolerated. Both regimens were effective in the treatment of newly diagnosed multiple myeloma patients. Further studies are required to determine the role of thalidomide in these two regimens.