ObjectiveTo systematically review the efficacy of double autologous hematopoietic stem cell transplantation (ASCT) in newly diagnosed multiple myeloma (NDMM). Methods PubMed, EMbase, The Cochrane Library, CNKI, and WanFang Data databases were electronically searched to collect randomized controlled trials (RCTs) on double ASCT for NDMM from inception to February 2021. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Meta-analysis was then performed by RevMan 5.3 software. Results A total of 6 RCTs involving 2 226 NDMM patients were included. The results of meta-analysis indicated that compared with single ASCT, more patients who received double ASCT could achieve satisfactory partial response (VGPR) or better (RR=1.12, 95%CI 1.01 to 1.25, P=0.03). Double ASCT resulted in a higher progression-free survival (PFS) rate from the second year for high-risk patients (2-year: RR=0.49, 95%CI 0.28 to 0.86, P=0.01; 5-year: HR=0.61, 95%CI 0.43 to 0.85, P=0.004). There were no statistical differences in treatment-related mortality and 5-year overall survival between the two groups. ConclusionsCompared with single ASCT, double ASCT can improve the VGPR rate of NDMM patients and the PFS rate of high-risk patients with comparable toxicities. Due to limited quality and quantity of the included studies, more high-quality studies are needed to verify the above conclusions.