To evaluate the role of high-dose melphalan plus autologous stem-cell transplantation (ASCT) as consolidation therapy for patients with newly diagnosed multiple myeloma (NDMM) in the era of novel agents, we undertook this meta-analysis. Medline, Embase, the Cochrane controlled trials register, the SCI, ASH, EHA, and ASCO were searched for clinical trials including high-dose chemotherapy plus ASCT for patients with NDMM. Finally, we identified four RCTs of ASCT versus novel agents based consolidations, and 10 single-arm prospective trials of ASCT alone. Pooled analysis indicated that response quality improved further after ASCT in the era of novel agents (≥CR rates of 13% pre-ASCT versus 29% post-ASCT, p =.003). When compared to novel agents containing consolidation regimens, high-dose chemotherapy plus ASCT significantly improved progression-free survival (PFS) (HR =0.56, p <.001). No significant difference in overall survival (OS) was found between them (HR =0.66, p =.22). Of note, subgroup analysis indicated that ASCT could significantly improve OS (HR =0.49, p =.0004) when compared to alkylating agent-based regimens plus lenalidomide consolidation. In summary, response quality and PFS improved further over ASCT in the era of novel agents. ASCT could improve survival than alkylating agent-based regimens plus lenalidomide consolidations for patients with NDMM. [ABSTRACT FROM AUTHOR]