cLimited therapeutic options exist for the treatment of vancomycin-resistant Enterococcus (VRE) bacteremia; the most commonly used are daptomycin and linezolid. We attempted a systematic review and meta-analysis of the comparative efficacy of those two agents. Studies comparing daptomycin to linezolid treatment for VRE bacteremia, published until August 2012, were identified from the MEDLINE, EMBASE, CENTRAL, ISI Web of Science, and SCOPUS databases. All comparative studies on patients older than 18 years of age that provided mortality data were considered eligible for this systematic review and meta-analysis. ⌻he primary outcome of the meta-analysis was 30-day all-cause mortality. Ten retrospective studies including 967 patients were identified. Patients treated with daptomycin had significantly higher 30-day all-cause mortality (odds ratio [OR], 1.61; 95% confidence interval [CI], 1.08 to 2.40) and infection-related mortality (OR, 3.61; 95% CI, 1.42 to 9.20) rates than patients treated with linezolid. When data from all 10 studies were combined, overall mortality was also significantly increased among patients treated with daptomycin (OR, 1.41; 95% CI, 1.06 to 1.89). These findings were confirmed when odds ratios adjusted for potential confounders were pooled. Relapse rates among patients treated with daptomycin were also higher (OR, 2.51; 95% CI, 0.94 to 6.72), although this difference did not reach statistical significance. Adverse event rates were not significantly different between the two groups. Notwithstanding the absence of randomized prospective data, available evidence suggests that mortality rates may be higher with daptomycin than with linezolid among patients treated for VRE bacteremia. E nterococci are the third most common cause of health careassociated bloodstream infections (BSIs) (1). Vancomycin is the first-line treatment of BSIs caused by ampicillin-resistant enterococci; however vancomycin-resistant enterococci (VRE) nowadays account for approximately one-third of the enterococcal health care-associated infections in the United States (2) and for more than 20% of such infections in some European countries (3). Mortality rates in patients with VRE BSIs range between 20 and 46% (4-6). Patients with BSI due to VRE are 2.5 times more likely to die than patients with BSI due to vancomycin-susceptible strains (7).Treatment of VRE BSIs is particularly challenging. Strains causing such infections are usually resistant to ampicillin (8), and therapeutic options include linezolid, daptomycin, quinupristindalfopristin, tigecycline, teicoplanin, and telavancin (for which limited clinical data are available). Teicoplanin is not available in the United States and can only be used for some VRE infections (i.e., strains with the VanB [vancomycin-resistant, teicoplaninsusceptible] phenotype and the rare species Enterococcus gallinarum and E. casseliflavus). Tigecycline does not achieve high serum concentrations and has not been approved for treatment of bacteremias (9). Use of quinupristin-dalfopristin (ef...