Previous studies have shown that bacteremia due to vancomycin-resistant Enterococcus species (VRE) is associated with mortality of 17%-100%, but comorbid conditions may have confounded the estimates. We designed a historical cohort study to determine the mortality attributable to VRE bacteremia. Twenty-seven patients with VRE bacteremia were identified as cases. Within 7 days of the onset of bacteremia, severe sepsis developed in 12 patients (44%) and septic shock developed in 10 (37%). Case patients were closely matched to control patients without VRE bacteremia (1:1) by time of hospitalization, duration of exposure, underlying disease, age, gender, and surgical procedure. The mortality was 67% among cases and 30% among matched controls (P = 0.1). Thus, the mortality attributable to VRE bacteremia was 37% (95% confidence interval [CI], 10%-64%) and the risk ratio for death was 2.3 [CI, 1.2-4.1). We conclude that VRE bacteremia is associated with high rates of severe sepsis and septic shock. The attributable mortality approaches 40%, and patients who have VRE bacteremia are twice as likely to die than closely matched controls.