Vancomycin (VCM) and daptomycin (DAP) are standard therapies for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia, despite concerns regarding clinical utility and growing resistance. Linezolid (LZD) affords superior tissue penetration to VCM or DAP and has been successfully used as salvage therapy for persistent MRSA bacteremia, indicating its utility as a first-choice drug against MRSA bacteremia. In a systematic review and meta-analysis, we compared the effectiveness and safety of LZD with VCM, teicoplanin (TEIC), or DAP in patients with MRSA bacteremia. We evaluated all-cause mortality as the primary effectiveness outcome, clinical and microbiological cure, hospital length of stay, recurrence, and 90-day readmission rates as secondary effectiveness outcomes, and drug-related adverse effects as primary safety outcomes. We identified 5328 patients across 2 randomized controlled trials (RCTs), 1 pooled analysis of 5 RCTs, 1 subgroup analysis (1 RCT), and 5 case-control and cohort studies (CSs). Primary and secondary effectiveness outcomes were comparable between patients treated with LZD versus VCM, TEIC, or DAP in RCT-based studies and CSs. There was no difference in adverse event incidence between LZD and comparators. These findings suggest that LZD could be a potential first-line drug against MRSA bacteremia as well as VCM or DAP.