The impact of active surveillance of patients at risk for infection with vancomycin-resistant enterococci (VRE) was examined, and VRE bacteremia rates and the degree of VRE clonality in 2 similar neighboring hospitals were compared. Hospital A did not routinely screen patients for VRE rectal colonization; hospital B actively screened high-risk patients. Retrospective observations were made over the course of 6 years, beginning when initial VRE bloodstream isolates were recovered at each institution. The rate of VRE bacteremia was 2.1-fold higher at hospital A, and the majority of hospital A isolates were clonally related: 4 clones were responsible for infection in >75% of patients with VRE bacteremia, and isolates from 30% of patients were from the most common clone. The 4 most common clones at hospital B were responsible for infection in 37% of patients, and isolates from 14.5% of patients were from the most common clone. Lower VRE bacteremia rates and a more polyclonal population, representing less horizontal transmission, may result from routine screening of patients who are at risk for VRE and prompt contact isolation of colonized individuals.