BACKGROUND: Vancomycin-resistant enterococci (VRE) are nosocomial pathogens in many U. S. hospitals. OBJECTIVE: To determine whether enhanced infection-control strategies reduce transmission of VRE in an endemic setting. DESIGN: Prospective cohort study. SETTING: Adult oncology inpatient unit. PATIENTS: 259 patients evaluated during use of enhanced infection-control strategies and 184 patients evaluated during use of standard infection-control practices. INTERVENTIONS: Patient surveillance cultures were taken, patients were assigned to geographic cohorts, nurses were assigned to patient cohorts, gowns and gloves were worn on room entry, compliance with infection-control procedures was monitored, patients were educated about VRE transmission, patients taking antimicrobial agents were evaluated by an infectious disease specialist, and environmental surveillance was performed. MEASUREMENTS: VRE infection rates, VRE colonization rates, and changes in antimicrobial use. RESULTS: During use of enhanced infection-control strategies, incidence of VRE bloodstream infections decreased significantly (0.45 patients per 1000 patient-days compared with 2.1 patients per 1000 patient-days; relative rate ratio, 0.22 [95% CI, 0.05 to 0.92]; P = 0.04), as did VRE colonization (10.3 patients per 1000 patient-days compared with 20.7 patients per 1000 patient-days; relative rate ratio, 0.5 [CI, 0.33 to 0.75]; P < 0.001). Use of all antimicrobial agents except clindamycin and amikacin was significantly reduced. CONCLUSION: Enhanced infection-control strategies reduced VRE transmission in an oncology unit in which VRE were endemic.