The aim of the study was to perform a meta-analysis of the efficacy and safety of (bortezomib plus lenalidomide/thalidomide)- vs (bortezomib or lenalidomide/thalidomide)-containing regimens as induction therapy in newly diagnosed multiple myeloma. We searched electronic and printed sources for relevant articles published. Inclusion criteria was as follows: randomized controlled trials (RCT) of (bortezomib plus lenalidomide/thalidomide) vs (bortezomib or lenalidomide/thalidomide)-containing regimens as induction therapy in newly diagnosed multiple myeloma. Two reviewers independently assessed potentially eligible studies and extracted relevant data. We retrieved five RCT studies including a total of 1,200 patients. Using the random-effects model to pool the five RCT with a statistically significant heterogeneity (P = 0.03; X 2 = 10.69; df = 4; I 2 = 63 %), the weighted risk ratios of a complete response (CR) for (bortezomib plus lenalidomide/thalidomide)-containing regimens was 1.81 (P = 0.005; 95 % CI: 1.20–2.73). When we excluded the study by Cavo et al. (Lancet 376:2075–2085, 2010), the pooled risk ratio for CR was 1.59 (P < 0.0001, 95 %CI: 1.29–1.96) with no statistically significant heterogeneity (P = 0.54; X 2 = 2.14; df = 3; I 2 = 0 %) among four RCT under the fixed effects mode. The pooled odds ratio for the main grade III/IV adverse events (the peripheral neuropathy, thrombotic events, and infections) were 1.76 (P = 0.32; 95 % CI: 0.58–5.31), 0.92 (P = 0.76, 95 %CI: 0.52–1.61), and 1.05 (P = 0.82, 95 % CI: 0.70–1.57), respectively. Our analysis showed (bortezomib plus lenalidomide/thalidomide)-containing regimens as induction treatment in newly diagnosed multiple myeloma improved CR but did not increase the risk of major adverse events (the peripheral neuropathy, thrombotic events, and infections).