Limited therapeutic options exist for the treatment of vancomycin-resistant Enterococcus (VRE) bacteraemia; the most commonly used are daptomycin and linezolid. We attempted a systematic review and meta-analysis on the comparative efficacy of those two agents. Studies comparing daptomycin to linezolid treatment for VRE bacteraemia, published until August 2012 were identified from MEDLINE, EMBASE, CENTRAL, ISI Web of Science and SCOPUS databases. All comparative studies on patients older than 18 years old that provided mortality data were considered eligible for this systematic review and meta-analysis. Τhe 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 (OR: 1.61, 95% CI: 1.08 to 2.40) and infection-related mortality (OR: 3.61, 95% CI: 1.42 to 9.20) rates compared to those treated with linezolid. When data from all ten 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 compared with linezolid among patients treated for VRE bacteraemia.