Background: Thalidomide is an immunomodulatory and anti-angiogenic drug that has shown promise in patients with myeloma.Trials comparing efficacy of standard melphalan and prednisone (MP) therapy with MP plus thalidomide (MPT) in transplant-ineligible or elderly patients with multiple myeloma (MM) have provided conflicting evidence.This meta-analysis aimed to determine the efficacy and toxicity of thalidomide in previously untreated elderly patients with myeloma.Methods: Medline, the Cochrane Controlled Trials register, conference proceedings of the American Society of Hematology (1995-2014), the American Society of Clinical Oncology (1995-2014), and CBM, VIP, and CNKI databases were searched for randomized control trials with the use of the medical subject headings MM and thalidomide.Trials were assessed by two reviewers for eligibility.Meta-analysis was conducted using a fixed effects model.Sensitivity analysis was performed to test the robustness of the findings.Results: Overall, seven trials were identified, covering a total of 1821 subjects.The summary hazard ratio (thalidomide vs.control) was 0.82 (95％ confidence interval [CI]: 0.72-0.94) for overall survival (OS), and 0.65 (95％ CI: 0.58-0.73) for progression-free survival, in favor of thalidomide treated group.The risk ratio of complete response with induction thalidomide was 3.48 (95％ CI: 2.24-5.41).A higher rate of Ⅲ/Ⅳ adverse events were observed in MPT arm compared with the MP arm.However, analysis of sub-groups administering anticoagulation as venous thromboembolism prophylaxis suggested no difference in relative risk of thrombotic events between two arms (RR =1.47, 95％ CI: 0.43-5.07, P =0.54).Further analysis of trials on the treatment effects of MPT versus MP on adverse events-related mortality showed no statistical difference between two arms (RR =1.24, 95％ CI: [0.95-1.63], P =0.120).Conclusion: Thalidomide appears to improve the OS of elderly and/or transplant-ineligible patients with MM when it is added to standard MP therapy.