Enterococci are the third leading cause of infectious endocarditis, and despite advances in diagnosis and treatment, the mortality of enterococcal endocarditis has not changed in recent decades. Although variables such as advanced age, cardiac failure, and brain emboli have been recognized as risk factors for mortality, cooperative multi-institutional studies have not assessed the role of other variables, such as nosocomial acquisition of infection, the presence of comorbidities, or the changing antimicrobial susceptibility of enterococci, as factors determining prognosis.We conducted the current study to determine the risk factors for mortality in patients with enterococcal endocarditis in a single institution. We reviewed 47 consecutive episodes of enterococcal endocarditis in 44 patients diagnosed according to the modified Duke criteria from a retrospective cohort study of cases of infectious endocarditis. The main outcome measure was inhospital mortality. We applied stepwise logistic regression analysis to identify risk factors for mortality.Predisposing heart conditions were observed in 86.3% of patients, and 17 had prosthetic valve endocarditis. A portal of entry was suspected or determined in 38.2%; the genitourinary tract was the most common source of the infection (29.7%). Comorbidities were present in 52.2% of cases. Twelve episodes (25.5%) were acquired during hospitalization. Only 3 isolates of Enterococcus faecalis were highly resistant to gentamicin. Eighteen patients (40.9%) needed valve replacement due to cardiac failure or relapse. Comparing cases of native valve and prosthetic valve endocarditis, we found no differences regarding complications, the need for surgical treatment, or mortality. Eight of 44 (18%) episodes were fatal. Age over 70 years (p = 0.05), heart failure (odds ratio [OR], 1.61; 95% confidence interval [CI], 1.15-2.25; p = 0.001), presence of 1 or more comorbidities (OR, 3.2; 95% CI, 1.11-9.39; p = 0.02), and nosocomial acquisition (OR, 8.05; 95% CI, 1.50-43.2; p = 0.01) were associated with mortality. In the multivariate analysis, only nosocomial acquisition increased the risk of mortality. In patients with enterococcal endocarditis, nosocomial acquisition of infection is an important factor determining outcome. As the incidence of bacteremia and the population of elderly people at risk continue to grow, the hazard of acquiring nosocomial enterococcal endocarditis may increase; hence, major emphasis must be put on prevention.