Background: Improper use of antibiotics in the past decades has lead to appearance of strains which are resistant to methicillin and vancomycin . Hospital personnel are the major source of infection and transmission of this bacterium. The aim this study was to determine the antibiotic susceptibility of to S.aureus isolated from personnel of Shiraz hospitals. Material and Methods: In this cross - sectional study in 1391,a total of 591 samples were collected from anterior nose of health care and health service workers of Shiraz hospitals. After identification of Staphylococcus aureus by biochemical and microbiological tests, antibiotic resistance patterns of isolates were investigated by disk diffusion method (CLSI) for 13 antibiotics. Minimum inhibitory concentration (MIC) values for vancomycin ,ticoplanin, linezolid and Quinupristin-Dalfopristin were assayed by E-test method (Liofilechem, Itly). Results: In this study14.6% of people were carriers of Staphylococcus aureus in their nose. 74% were health care workers and 26% were health service personnel. There was not statistically significant relation between being a nasal carrier with different jobs, wards or sex of personnel (p>0.05). The lowest resistance was seen for vancomycin, tiecoplanin, linezolid and Quinupristin-Dalfopristin (95.3%) and the high resistant antibiotic were amoxicillin and ampicillin (3.5%). In E-test method only two isolate was resistant to vancomycin. Only two strains were resistant to vancomycin in E-test method. Conclusion: As 14.6% of personnel in this study were carriers of Staphylococcus aureus and the isolates were resistant to most common antibiotics, thus determination of antibiotic resistance patterns for these resistant strains from hospital personnel can prevent nosocomial infections.