Infections due to methicillin-resistant Staphylococcus aureus bacteraemia (MRSAB) seriously threaten public health due to poor outcomes and high mortality. The objective of this study is to perform a systematic review and meta-analysis of the current evidence on adjuvant β-lactam (BL) therapy combined with vancomycin (VAN) or daptomycin (DAP) for MRSAB. PubMed, Embase and Cochrane Library were systematically searched for publications reporting clinical outcomes of BLs+VAN or BLs+DAP for adult patients with MRSAB through April 5, 2020. Meta-analysis techniques were applied using random-effects modelling. Three randomized controlled trials and 12 retrospective cohort studies were identified, totalling 2594 patients. Combination treatment significantly reduced the risk of clinical failure [lsqb]risk ratio (RR)=0.80, 95% confidence interval (CI) 0.66-0.96; P=0.02, I2=39%[rsqb], bacteraemia recurrence (RR=0.66, 95% CI 0.50-0.86; P=0.002, I2=0%), and persistent bacteraemia (RR=0.65, 95% CI 0.55-0.76; P<0.00001, I2=0%) and shortened the duration of bacteraemia [lsqb]standardized mean difference(SMD)= -0.37, 95% CI -0.48 to -0.25; P<0.00001, I2=0%[rsqb]. There was no significant difference in the risk of crude mortality, nephrotoxicity, or thrombocytopenia between groups. Notably, combination treatment might non-significantly increase the risk of C. difficile infection (CDI) (RR=2.13, 95% CI 0.98-4.63; P=0.06, I2=0%). Subgroup analysis suggested that DAP+BLs could reduce crude mortality (RR=0.53,95% CI 0.28-0.98; P=0.04,I2=0%).The meta-analysis suggested that although combination therapy with BLs could improve some microbial outcomes, it could not reduce crude mortality but might increase the risk of CDI and should be applied very cautiously. Regarding mortality reduction, the combination of DAP+cephalosporins appears more promising. Copyright © 2020 Wang et al.