Vancomycin-resistant Enterococcus bloodstream infections (VRE-BSI) are a growing problem with few clinical trials to guide therapy. We conducted a retrospective study of management and predictors of mortality for VRE-BSI at a tertiary-care centre from January 2005 to August 2008. Univariate and multivariable analyses examined the relationship of patient characteristics and antibiotic therapy with 30-day all-cause mortality. Rates of VRE-BSI increased from 0·06 to 0·17 infections/1000 patient-days (P=0·03). For 235 patients, 30-day mortality was 34·9%. Patients were primarily treated with linezolid (44·2%) or daptomycin (36·5%). Factors associated with mortality were haemodialysis [odds ratio (OR) 3·2, 95% confidence interval (CI) 1·6-6·3, P=0·007], mechanical ventilation (OR 3·7, 95% CI 1·3-10·4, P=0·01), and malnutrition (OR 2·0, 95% CI 1·0-4·0, P=0·046). Use of linezolid, but not daptomycin (P=0·052) showed a trend towards an association with survival. In conclusion, VRE-BSI is a growing problem, associated with significant 30-day mortality. Multiple factors were associated with poor outcomes at our hospital. © Copyright Cambridge University Press 2010.