ABSTRACT: Objective:In this study, we evaluated the effectiveness of a management bundle for Enterococcus spp bloodstream infection (E-BSI). Method:This was a single-center, quasi-experimental (pre/post) study. In the prephase (January 2014 to December 2015), patients with monomicrobial E-BSI were retrospectively enrolled. During the post- or intervention phase (January 2016 to December 2017), all patients with incident E-BSI were prospectively enrolled in a nonmandatory intervention arm comprising infectious disease consultation, echocardiography, follow-up blood cultures, and early targeted antibiotic treatment. Patients were followed up to 1 year after E-BSI. The primary outcome was 30-day mortality. Results:Overall, 368 patients were enrolled, with 173 in the prephase and 195 in the postphase. The entire bundle was applied in 15% and 61% patients during the pre- and postphase, respectively (P < .001). Patients enrolled in the postphase had a significant lower 30-day mortality rate (20% vs 32%, P = .0042). At multivariate analysis, factors independently associated to mortality were age (hazard ratio [HR], 1.03; 95% confidence interval [CI], 1.00-1.05), intensive care unit admission (HR, 2.51; 95% CI, 1.18-3.89), and healthcare-associated (HR, 2.32; 95% CI, 1.05-5.16) and hospital-acquired infection (HR, 2.85; 95% CI, 1.34-4.76), whereas being enrolled in the postphase period (HR, 0.49; 95% CI, 0.32-0.75) was associated with improved survival. Results were consistent also in the subgroups with severe sepsis (HR, 0.37; 95% CI, 0.16-0.90) or healthcare-associated infections (HR, 0.53; 95% CI, 0.31-0.93). A significantly lower 1-year mortality was observed in patients enrolled in the postphase period (50% vs 68%, P < .001). Conclusions:The introduction of a bundle for the management of E-BSI was associated with improved 30-day and 1-year survival.