Objective To analyze the spatiotemporal distribution of clinically isolated vancomycin-resistant Enterococcus faecium (VR-Efm) in Guangdong Province in recent years, and explore the causes for the increase in VR-Efm detection rate. Methods A retrospective analysis was conducted on the data about the detection, patients' demographic characteristics, as well as departments and specimens distribution of VR-Efm reported to Guangdong Province Antimicrobial Resistance Surveillance System by 38 medical institutions in 4 regions of Guangdong Province (Pearl River Delta, East Guangdong, West Guangdong, and North Guangdong) in 2019-2023. The detection of 5 other antimicrobial-resistant ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter species) concerned by World Health Organization was analyzed synchronously. Results The detection rate of VR-Efm in Guangdong Province increased from 1.4%(63/4 543) in 2019 to 21.3% (1 351/6 345) in 2023, showing a significant upward trend. In 2023, 44.7% (n=17) medical institutions had a VR-Efm detection rate of >20%; the detection rate of VR-Efm in 4 regions of Guangdong Province has generally increased, with a radiation increase from the Pearl River Delta region to the surrounding areas. The overall ESKAPE increased from 10.1% in 2019 to 10.8% in 2023. Among the other 5 pathogens, the detection rate of carbapenem-resistant Klebsiella pneumoniae increased from 8.0% in 2019 to 15.0% in 2023. The detection rates of carbapenem-resistant Acinetobacter baumannii, methicillin-resistant Staphylococcus aureus, carbapenem-resistant Pseudomonas aeruginosa, and carbapenem-resistant Enterobacter spp. decreased from 61.6%, 34.4%, 21.2%, and 7.9% in 2019 to 58.2%, 31.9%, 21.0%, and 7.6% in 2023, respectively, all showed varying degrees of decline. The detection rate of VR-Efm in intensive care unit (ICU) (12.2%) was higher than that in non-ICU departments such as outpatient and emergency department (9.4%), internal medicine department (9.2%) and surgery department (7.0%) (all P < 0.05). The specimens with higher detection rates of VR-Efm were urine (9.8%) and blood (9.1%), while the detection rates of other specimens ranged from 6.9% to 9.6%. The detection rate of VR-Efm from adolescent patients was lower than that of middle-aged and elderly patients (4.4% vs >9.4%, P < 0.05). Conclusion In the past 5 years, the detection rate of VR-Efm in Guangdong Province has significantly increased, which may be related to the transmission of dominant clone acquired from communities and hospitals. Medical institutions with favorable condition should conduct VR-Efm screening for hospitalized patients, take effective prevention and control measures for patients with VR-Efm, so as to curb the increase in detection rate of VR-Efm in the region.