Background:Today, significant increase in the prevalence and emergence of methicillin-resistant Staphylococcus aureus (MRSA) is a serious public health concern and is likely to have a dramatic negative impact on many current medical practices. Therefore, identification of MRSA strains is important for both clinical and epidemiological implications.Objectives:The present study was carried out to determine the frequency of methicillin resistant; antibiotic susceptibility and plasmid profiles of S. aureus recovered from different types of clinical samples of patients in Zabol, Iran.Material and Methods:Clinical samples from 500 outpatient and hospitalized patients were tested for S. aureus. The susceptibility of 106 S. aureus to 11 antibiotics was evaluated by the disk diffusion method and Etest oxacillin strips. The presence of mecA gene was investigated by polymerase chain reaction (PCR). The plasmid profile patterns of all isolates were determined by a modified alkaline lysis method.Results:A total of 67 (63.20%) strains were found to be MRSA isolates. Most of MRSA isolates showed high level of resistance to ampicillin, erythromycin, nalidixic acid, penicillin, and tetracycline. Twenty-six percent of MRSA isolates showed high level of resistance to oxacillin (minimum inhibitory concentration [MIC] ≥ 256 μg/mL). mecA gene was detected among 62 MRSA isolates. Totally, 75 isolates of both strains harbored plasmid.Conclusions:Resistance to oxacillin and other antibiotics was high, and most of the isolates were found to be multi-drug resistance (MDR). Plasmid analysis of representative S. aureus isolates also demonstrates the presence of a wide range of plasmid sizes, with no consistent relationship between plasmid profiles and resistance phenotypes. Regular surveillance of hospital infections and monitoring of their antibiotic sensitivity patterns are required to reduce MRSA prevalence. High prevalence and multi-drug resistance of MRSA isolates in southeast of Iran could be considered as an urgent warning for public health.