OBJECTIVE: To describe the evolving epidemiology and risk associations of vancomycin-resistant Enterococcus (VRE) between 2018 and 2023 in a tertiary hospital in Singapore. METHODS: Inpatients in Singapore General Hospital (SGH) between January 2018 and December 2023 were included. VRE surveillance criteria changed in August 2020 and November 2022. Incidence of any VRE (VRE (all)), VRE from surveillance (VRE (surveillance)), clinical VRE isolates (VRE (clinical)), healthcare-associated VRE infections (HA-VRE (infections)) and bacteremia (VRE (bacteremia)) were reviewed. Three case-control studies were conducted. Environmental screening was performed. RESULTS: Over the six-year study period there were 5,173 patients with VRE, of whom 3,141 (60.7%) had HA-VRE, 5157 (99.7%) had E.faecium and 4,336 (84%) carried vanA.121 (2.2%) patients had VRE bacteraemia with mortality 50.4%. There were significant changes in incidence of VRE (all), VRE (surveillance) and VRE (clinical) but HA-VRE (infections) and VRE (bacteremia) remained stable. VRE acquisition was associated with presence of concurrent MRSA (OR 9.4, 95% CI 1.3-66.8, p-value <
0.02), CPE (OR 7.2, 95% CI 2.0-26.0, p-value <
0.001), ICU admission (OR 6.1, 95% CI 2.8-13.2, p<
0.001), hemodialysis (OR 4.6, 95% CI 1.8-12.0, p<
0.001), surgery (OR 3.7, 95% CI 1.6-8.3, p<
0.001), vancomycin use (OR 28.2, 95% CI 5.4-146.5, p<
0.001) and metronidazole use (OR 4.4, 95% CI 1.0-19.0, p-value 0.04) in the preceding three-months. VRE infection had similar risk associations. 12.5% of environmental samples were VRE positive. CONCLUSION: VRE endemic state in SGH is associated with significant patient and environmental VRE burden. VRE acquisition and infection have been associated with co-carriage of MRSA or CPE, vancomycin and metronidazole use, ICU admission and prior surgery. Targeted infection prevention and antimicrobial-stewardship programs may reduce VRE (infections).