Background & objectives: Growing incidence of methicillin resistant Staphylococcus aureus (MRSA) and vancomycin resistant enteroccoci (VRE) is posing a therapeutic problem due to limited drug options. Therefore, the present study was undertaken to check susceptibility of MRSA and VRE isolates against new antimicrobials such as daptomycin and linezolid. Methods: A total of 586 Gram-positive isolates comprising 442 S. aureus and 144 enterococci isolated from hospitalized cases included in the study, were subjected to in vitro antimicrobial susceptibility testing by disc diffusion method. One hundred twenty four enterococci obtained from rectal swabs of neonates were also included. Minimum inhibitory concentration (MIC) was determined for daptomycin, linezolid, vancomycin and teicoplanin against 50 each isolates of MRSA and VRE by E strip. Results: Among the staphylococci, 326 (73.85%) isolates were MRSA. MIC for vancomycin and teicoplanin among MRSA was ≤ 3 μg/ml. MIC for daptomycin among MRSA was found to be in the range of 0.064-1.5 μg/ml. Percentage of VRE among clinical samples was 14.29 per cent while it was 47.06 per cent among enterococci from rectal swabs of neonates. MIC was >256 μg/ml for vancomycin among VRE and was associated with van A genotype. MIC range for daptomycin among VRE was 0.38-3 μg/ml. MIC for linezolid among MRSA and VRE was in the range of 0.25 to 1 and 0.38 -1.5 μg/ml, respectively. Interpretation & conclusions: The present study showed a rise in MIC to vancomycin for sizable number of MRSA and growing percentage of VRE at our centre. Daptomycin and linezolid showed 100 per cent activity against MRSA and VRE.