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Background/Purpose: Vancomycin-resistant Enterococcus (VRE), a multidrug-resistant, difficult-to-treat pathogen of healthcare-associated infections (HAIs), is now endemic at many intensive care units (ICUs). Chlorhexidine (CHG) bathing is a simple and highly effective intervention to decrease VRE acquisition, but its effect on VRE-HAIs has not been assessed in prospective studies at ICUs. Methods: This is a cluster quasi-experimental controlled study. Under active VRE surveillance and contact isolation of all identified VRE carriers, four ICUs were assigned to provide 2% CHG bathing for all patients on a daily basis (CHG group) during the intervention period, while another four ICUs were assigned to provide standard care without CHG bathing for all patients (standard care group) during the same period. Results: The CHG group (n = 1501) had a 62% lower crude incidence of VRE-HAIs during the intervention period, compared with the baseline period (1.0 vs. 2.6 per thousand patient-days, P = 0.009), while VRE-HAIs incidence did not change in standard care group (n = 3299) (1.1 vs. 0.5 per thousand patient-days, P = 0.139). In multivariable analyses, CHG bathing was independently associated with a 70% lower risk of VRE-HAIs (adjusted odds ratio [OR] 0.3, 95% confidence interval [CI], 0.2 to 0.7, P = 0.006). In contrast, standard care during the same period had no effect on the risk of VRE-HAIs (adjusted OR 1.8, 95% CI: 0.7 to 4.7, P = 0.259). Conclusion: CHG bathing is a highly effective approach to prevent VRE-HAIs at ICUs, in the context of active VRE surveillance with contact isolation.