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This study explored the prevalence of multi-drug resistance and virulence factors of enterococcal isolates obtained from various clinical specimens (<i>n</i> = 1575) including urine, blood, pus, tissue, catheter, vaginal wash, semen, and endotracheal secretions. Out of 862 enterococcal isolates, 388 (45%), 246 (29%), 120 (14%), and 108 (13%) were identified as <i>Enterococcus faecalis</i>, <i>Enterococcus faecium</i>, <i>Enterococcus durans</i>, and <i>Enterococcus hirae</i>, respectively, using standard morphological and biochemical methods. The antibiotic resistance profile of all these enterococcal isolates was checked using the disc diffusion technique. High-level resistance was observed for benzylpenicillin (70%) and vancomycin (43%) among <i>E. faecalis</i> and <i>E. faecium</i> isolates, respectively. This study also revealed the prevalence of ‘multi-drug resistance (resistant to 3 antibiotic groups)’ among the vancomycin-resistant enterococcal strains, and this was about 11% (<i>n</i> = 91). The virulence determinants associated with vancomycin resistance (VR) were determined phenotypically and genotypically. About 70 and 39% of <i>E. faecalis</i> and <i>E. faecium</i> isolates showed to be positive for all four virulence factors (gelatinase, protease, hemolysin, and biofilm). Among the several virulence genes, <i>gelE</i> was the most common virulence gene with a prevalence rate of 76 and 69% among <i>E. faecalis</i> and <i>E. faecium</i> isolates, respectively. More than 50% of VRE isolates harbored other virulence genes, such <i>esp</i>, <i>asa</i>, <i>ace</i>, and <i>cylA</i>. Similarly, the majority of the VR enterococcal isolates (<i>n</i> = 88/91) harbored <i>vanA</i> gene and none of them harbored <i>vanB</i> gene. These results disclose the importance of VR <i>E. faecalis</i> and <i>E. faecium</i> and the associated virulence factors involved in the persistence of infections in clinical settings.