The aim of the study was to evaluate the clinical efficacy and safety of bortezomib-based regimens for the treatment of multiple myeloma through meta-analysis. The literature on three classes of bortezomib-based regimens – bortezomib and thalidomide (VT), bortezomib and lenalidomide (VR) and bortezomib and doxorubicin (VD) – was systematically retrieved and analyzed. The initial search yielded 4896 citations, of which 14 randomized controlled trials (RCTs) (a total of 5379 patients enrolled) met the pre-specified inclusion criteria. The results indicated that the VT regimen had an improved benefit in complete remission (CR) and overall response rate (ORR), but not in progression-free survival (PFS), overall survival (OS) and major grade III/IV adverse events such as peripheral neuropathy, thrombotic events and infection. In contrast, the VD regimen had an improved CR with fewer thrombotic events, while PFS, OS, ORR and the other adverse events showed no significant difference. No significant difference was observed in CR, ORR and major grade III/IV adverse events when comparing the VR regimen with bortezomib and cyclophosphamide (VC), but patients receiving VR regimen therapy had obviously longer PFS and OS.