The incidence of enterococcal bacteremia due to Enterococcus faecium is increasing. To understand the clinical significance of E. faecium bacteremia, we compared 16 patients who were bacteremic due to E. faecium to 56 patients who were bacteremic due to Enterococcus faecalis. E. faecium bacteremia developed most frequently in severely ill patients with fever or hypothermia accompanied by CNS, cardiovascular, and/or pulmonary dysfunction, while E. faecalis bacteremia occurred most often in less seriously ill patients. Nosocomial acquisition, cancer, neutropenia, renal insufficiency, current corticosteroid therapy, and previous treatment with broad-spectrum antibiotics were significantly more frequently associated with E. faecium bacteremia. Mortality was significantly higher among patients infected with E. faecium than among those infected with E. faecalis (50% vs. 11%; P = .001); this was true particularly among patients with monomicrobial or nosocomial bacteremia, those who had previously received antibiotic treatment, and those with cancer. Death due to enterococcal bacteremia was observed only among severely ill patients. These findings suggest that E. faecium often infects debilitated patients and that such infection appears to be a significant factor contributing to mortality.