Vancomycin combined with β-lactams (Combo therapy) has been encouraged in the treatment of Methicillin-resistant Staphylococcus aureus(MRSA) bloodstream infections (BSIs) in recent years, but its efficacy and safety have not been systematically evaluated. This study performed a systematic review and meta-analysis to clarify the efficacy and safety of Combo therapy in patients with MRSA BSIs. Relevant articles reporting on the clinical or microbiology outcomes of Combo treatment in adult patients with MRSA bacteremia throughout November 2019 were searched in PubMed,EMBASE and Cochrane Library databases. Summary odds ratios (ORs) or mean differences (MDs) and 95% confidence intervals (CIs) were evaluated using a fixed- or random-effects model. Six articles (806 patients) consisting of one RCT and five retrospective cohort studies were included in this study. The pooled data showed that Combo therapy could significantly reduce the risk of microbiological failure (OR = 0.54, 95% CI 0.35-0.83, I2 40%, P = 0.005) and persistent bacteremia (OR = 0.48, 95% CI 0.30-0.77, I2 13%, P = 0.002) as well as shorten the duration of bacteremia (MD= -1.06, 95% CI -1.53- -0.60, I2 0%, P＜0.00001). In addition, it did not significantly increase the incidence of nephrotoxicity (OR = 1.17, 95% CI 0.64-2.13, I2 0%, P = 0.61). However, no significant difference was detected between the groups regarding 28/30-day mortality, MRSA-related mortality, bacteremia relapse, or length of hospitalization. These results demonstrate that Combo therapy clears the pathogenic bacteria of MRSA bacteremia but does not improve the clinical prognosis. Since the sample size was small and most of the studies were retrospective cohort studies with substantial heterogeneity, there is a need for further studies encompassing large-scale multicenter RCTs to validate our results. Copyright © 2020. Published by Elsevier Ltd.