Bloodstream infections due to vancomycin-resistant enterococci (VRE-BSI) result in substantial patient mortality and cost. Daptomycin and linezolid are commonly prescribed for VRE-BSI, but there are no clinical trials to determine optimal antibiotic selection. We conducted a systematic review for investigations that compared daptomycin and linezolid for VRE-BSI. We searched Medline from 1966 through 2012 for comparisons of linezolid and daptomycin for VRE-BSI. We included searches of EMBASE, clinicaltrials.gov, and national meetings. Data were extracted using a standardized instrument. Pooled odds ratios (OR) and 95% confidence intervals (95% CI) were calculated using a fixed-effects model. Our search yielded 4,243 publications, of which 482 contained data on VRE treatment. Most studies (452/482) did not present data on BSI or did not provide information on linezolid or daptomycin. Among the remaining 30 studies, 9 offered comparative data between the two agents. None were randomized clinical trials. There was no difference in microbiologic (n ‫؍‬ 5 studies, 517 patients; OR, 1.0; 95% CI, 0.4 to 1.7; P ‫؍‬ 0.95) and clinical (n ‫؍‬ 3 studies, 357 patients; OR, 1.2; 95% CI, 0.7 to 2.0; P ‫؍‬ 0.7) cures between the two antibiotics. There was a trend toward increased survival with linezolid compared to daptomycin treatment (n ‫؍‬ 9 studies, 1,074 patients; OR, 1.3; 95% CI, 1.1 to 1.8; I 2 ‫؍‬ 0 [where I 2 is a measure of inconsistency]), but this did not reach statistical significance (P ‫؍‬ 0.054). There are limited data to inform clinicians on optimal antibiotic selection for VRE-BSI. Available studies are limited by small sample size, lack of patient-level data, and inconsistent outcome definitions. Additional research, including randomized clinical trials, is needed before conclusions can be drawn about treatment options for VRE therapy.