Introduction: Staphylococcus aureus is one of the most common human pathogen capable of causing a wide range of infections. Staphylococcus aureus is a common cause of both community and hospital infections. It was the endemic microorganism in several reports of nosocomial infections which induced high mortality and morbidity. This microorganism is a virulent bacterium that can cause serious infections including skin and soft tissue infections, wound infection, bacteremia, pneumonia and endocarditis. It is estimated that Staphylococcus aureus has developed the ability to acquire resistance to all classes of antimicrobial agents and methicillin-resistant S. aureus (MRSA) has become a major problem in many hospitals worldwide. Hospital acquired infection (HAI) due to multidrug resistant bacteria like MRSA are a growing problem in many health care institutes. Materials and Method: A total of 568 clinical isolates of Staphylococcus aureus were isolated from various clinical specimens received in the Department of Microbiology, Sri Lakshmi Narayana Institute of Medical Sciences, Pondicherry from April 2014 to December 2017, were included in the study. Isolation and identification of Staphylococcus aureus was done by standard conventional microbiological methods. Identification of MRSA was done as per standard guidelines of CLSI by using Oxacillin broth microdilution method. Antibiogram was determined by Kirby-Bauer disc diffusion method on Mueller-Hinton agar with zones of inhibition. Results: Staphyloccus aureus was susceptible to Vancomycin (94.7%), followed by Teicoplanin (91.7%), Linezolid ( 88.5%), Amikacin (85.7%). In case of MRSA all the isolates showed 100% susceptibility to vancomycin, followed by Teicoplanin (97.5%), Amikacin (84.7%) linezolid (80.3%) and Clindamycin (54.8%). In case of MRSA all the isolates were 100% susceptible to vancomycin followed by teicoplanin (97.5%), amikacin (84.7%) linezolid (80.3%) and clindamycin (54.8%). Conclusion: MRSA infections are emerging as a serious health problem in health care set up. Joint efforts by clinicians, clinical microbiologists, hospital management and public health authorities are required to meet the challenge of MRSA on the forefront.