Background: Staphylococcus aureus particularly MRSA strains are one of the major causes ofrncommunity and hospital acquired bacterial infections. They are also becoming increasingly multi-rndrug resistant, and have recently developed resistance to vancomycin, which has been usedrnsuccessfully to treat MRSA for many years. In-vitro determination of drug resistance patterns of S.rnaureus is critical for the selection of effective drugs for the treatment of staphylococci infections.rnObjective: The aim of this study was to determine the prevalence of MRSA and MSSA strainsrnisolated from different clinical specimens from patients referred for routine culture and sensitivityrntesting and also to define the antimicrobial susceptibility pattern of the strains.rnMethod: A cross sectional study was conducted among 1360 study participants selected convenientlyrnat Yekatit 12 Hospital Medical College from September 2013 to April 2014. Clinical samples fromrnvarious anatomical sites of the study subjects were collected by employing standard microbiologicalrntechniques. Clinical samples were cultured on blood agar and mannitol salt agar and incubated at 35rn-370C aerobically for 18-24 hours. Cultures with typical characteristics of staphylococci werernidentified to S. aureus by using DNAse test. S. aureus isolates then were screened for MRSA byrnusing 1ïg oxacillin disc. The drug susceptibility patterns of both MRSA and MSSA to twelvernantibacterial drugs were determined by disc diffusion procedure. All S. aureus isolates examined forrnbeta-lactamase production by employing nitrocefin. Data were coded, entered and analyzed usingrnSPSS version 16 software and logistic regressions were applied to assess any association betweenrndependent and independent variables. P values < 0.05 were taken as statistically significant.rnResults: Of the1360 clinical specimens analyzed S. aureus was recovered from 194 (14.3%). Thernprevalence of S. aurues was higher in males than females 106 (54.6%) versus 88 (45.4%) and inrnpatients with age group of 25-44 years 64 (33.0%). However, the isolation rate of S. aureus was notrnsignificantly associated with sex (p = 0.77) and age group (p > 0.05)rnRate of isolation of S. aureus with regards to clinical specimens was the highest in pus 118 (60.8 %)rnand the lowest in sputum 1 (0.5%). Out of 194 S. aureus isolates, 34 (17.5%) were found out to bernMRSA and the remaining 160 (82.5%) were MSSA. Relatively a higher MRSA was observed inrnmales than females 19 (55.9%) versus 15 (44.1%) and in the age group 25-44 years 12 (35.3%). Nornsignificant association was observed between MRSA and sex (p= 0.87) and age groups (p> 0.05).rnNinety eight (50.5%) S. aureus were multi-resistant (resistant to three or more antimicrobial agents)rnand isolates were more resistant to penicillin 187(96.4%) and least resistant for vancomycin 10(5.1%)rnand cephalothin 6(3.0%). MRSA stains were 100% resistant to penicillin G, erythromycin,rntrimethoprim-sulfamethoxazole and least resistant to vancomycin 10(29.4%) and cephalothinrn6(17.6%). Out of 194 S. aureus isolates 153 (79%) were beta-lactames producers. Furthermore, of 34rnMRSA isolates 30 (88.2%) and out of 160 MSSA strains 123 (76.8%) produced beta-lactamase.rnConclusion: In this study Staphylococcus aureus isolates exhibited very high degree of resistance torndifferent antibiotics. The isolates were also multidrug resistant to several combinations of the testedrnantibiotics. The emergence of vancomycin resistant S. aureus highlights the value of prudentrnprescribing of antibiotics (including vancomycin) and avoiding their irrational use