Background: Vancomycin-resistant enterococcus (VRE) colonization and infection have increased at our hospital, despite adherence to standard VRE control guidelines. Aim: We implemented a multi-modal, hospital-wide improvement programme including a bleach-based cleaning-disinfection programme ( Bleach-Clean ). VRE colonization, infection and environmental contamination were compared pre and post implementation. Methods: The programme included a new product (sodium hypochlorite 1000 ppm + detergent), standardized cleaning-disinfection practices, employment of cleaning supervisors, and modified protocols to rely on alcohol-based hand hygiene and sleeveless aprons instead of long-sleeved gowns and gloves. VRE was isolated using chromogenic agar and/or routine laboratory methods. Outcomes were assessed during the 6 months pre and 12 months post implementation, including proportions (per 100 patients screened) of VRE colonization in high-risk wards (HRWs: intensive care, liver transplant, renal, haematology/oncology); proportions of environmental contamination; and episodes of VRE bacteraemia throughout the entire hospital. Findings: Significant reductions in newly recognized VRE colonizations (208/1948 patients screened vs 324/4035, a 24.8 reduction, P = 0.001) and environmental contamination (66.4 reduction, P = 0.012) were observed, but the proportion of patients colonized on admission was stable. The total burden of inpatients with VRE in the HRWs also declined (median percentage of colonized inpatients per week, 19.4 vs 17.3 , P = 0.016). Hospital-wide VRE bacteraemia declined from 14/2935 patients investigated to 5/6194 (83.1 reduction; P <0.001), but there was no change in vancomycin-susceptible enterococcal bacteraemia (P = 0.54). Conclusion: The Bleach-Clean programme was associated with marked reductions in new VRE colonizations in high-risk patients, and VRE bacteraemia across the entire hospital. These findings have important implications for VRE control in endemic healthcare settings.