Vancomycin-resistant Enterococcus faecium (VREF) has emerged as a relevant multidrug-resistant pathogen and potentially lethal etiology of health care associated infections worldwide. The objective of this retrospective cohort study was to assess factors associated with mortality in patients with VREF bacteremia in a major tertiary referral hospital in Southern Brazil. All documented cases of bacteremia identified between May 2010 and July 2012 were evaluated. Cox regression was performed to determine whether the characteristics related to the host or antimicrobial treatment were associated with the all-cause 30-day mortality. In total, 35 patients with documented VREF bacteremia were identified during the study period. The median APACHE-II score of the study population was 26 (interquartile range: 10). The overall 30-day mortality was 65.7%. All VREF isolates were sensitive to linezolid, daptomycin, and quinupristin-dalfopristin. Linezolid was the only antimicrobial agent with in vitro activity against VREF that was administered to the cohort. After multivariate analysis, linezolid treatment (HR, 0.08; 95% CI, 0.02–0.27) and presence of acute kidney injury at the onset of bacteremia (HR, 4.01; 95% CI, 1.62–9.94) were independently associated with mortality. Presentation with acute kidney injury and lack of treatment with an effective antibiotic poses risk for mortality in patients with VREF bacteremia.