Objective To understand the antimicrobial resistance of clinically isolated Enterococcus spp. in Hunan Province. Methods Surveillance data of Enterococcus spp. resistance from member units of Hunan Provincial Antimicrobial Resistance Surveillance System from 2012 to 2021 were collected. Data were cleaned according to a unified method, and WHONET 5.6 software was adopted for statistical analysis. Results From 2012 to 2021, a total of 110 652 non-repetitive Enterococcus spp. strains were included in the analysis, mainly Enterococcus faecalis and Enterococcus faecium, accounting for 46.9% (n=37 774) and 45.9% (n=36 968), respectively, followed by Enterococcus avium (2.5%, n=1 982), Enterococcus gallinarum (1.8%, n=1 428), and Enterococcus casseliflavus (1.5%, n=1 185). The main specimen sources of Enterococcus spp. was urine (51.8%, n=57 350), followed by secretions (9.6%, n=10 660) and bile (8.5%, n=9 377). From 2012 to 2021, the resistance rates of Enteroco-ccus faecalis to ampicillin, teicoplanin, and vancomycin were 5.5%-12.0%, 1.3%-2.0%, and 0.6%-1.4%, respectively. The resistance rates of Enterococcus faecium to ampicillin, teicoplanin, and vancomycin were 69.2%-85.0%, 1.5%-2.8%, and 0.7%-2.5%, respectively. Except for linezolid and minocycline, the resistance rates of Enterococcus faecium to tested antimicrobial agents were all higher than those of Enterococcus faecalis. The resistance rates of Enterococcus faecalis and Enterococcus faecium to vancomycin decreased from 1.4% and 2.1% in 2012 to 0.6% and 0.7% in 2021, respectively, presenting a decreased trend. Conclusion Clinically isolated Enterococcus spp. maintain high antimicrobial susceptibility to vancomycin and teicoplanin. Resistance rates of Enterococcus faecalis and Enterococcus faecium to vancomycin present decreased trends.