Introduction: Tigecycline is a potential therapeutic agent for multidrug resistant gram positive and gram negative organisms. The clinical efficacy of synergic combination of daptomycin with betalactam antibiotics have been described against various species of Enterococcus isolates. Aim: To detect the in-vitro activity of tigecycline and daptomycin against Enterococcus species and their antimicrobial activity with Vitek 2 automated system. Materials and Methods: This was a cross-sectional study conducted at Department of Microbiology, Vinayaka Mission's Kirupananda Variyar (VMKV) Medical College and Hospitals, Salem, Tamil Nadu, India. Isolates of Enterococcus obtained over a period of two years from March 2016 - March 2018 from various clinical samples were identified by standard biochemical method and their antimicrobial susceptibility pattern was determined. Minimum Inhibitory Concentration (MIC) of tigecycline and daptomycin was determined by Vitek 2 automated system. Analysis of data was done by using frequency distribution and percentage. Results: Out of 211 Enterococcus isolates studied, 23 (10.90%) isolates showed decreased susceptibility to daptomycin with MIC of >= 8 mu g/mL. All isolates showed 100% susceptibility to tigecycline. Conclusion: The present study showed potent antimicrobial activity of tigecycline against various species of Enterococcus. Decreased susceptibility to daptomycin has been observed among the study isolates. Further clinical investigations are required to know the potential benefits of these agents in therapy.