Background: <i>Staphylococcus aureus</i> particularly methicilin resistant <i>S. aureus</i> strains are one of the major causes of community and hospital acquired bacterial infections, often causing postoperative and burn wound infections. In-vitro determination of drug resistance patterns of <i>S. aureus</i> is critical for the selection of effective drugs for the treatment of staphylococci infections. Objective: The aim of this study was to determine methicillin and antimicrobial susceptibility pattern of <i>S. aureus</i> from postoperative and burn wound patients in Ethiopia. Materials and Methods: A cross sectional study was conducted among 378 patients at Yekatit 12 Hospital Medical College from September 2013 to August 2014 in Ethiopia. Swabs from postoperative and burn wound were collected. Swabs were cultured on blood agar and mannitol salt agar and incubated at 35-37°C aerobically for 18-24 hours. Cultures with typical characteristics were identified to <i>S. aureus</i> by DNAse agar test. <i>S. aureus</i> were then screened for MRSA using 30g cefoxitin disc. The drug susceptibility patterns of <i>S. aureus</i> to eleven drugs were determined by disc diffusion procedure and agar dilution for vancomycin. All <i>S. aureus</i> isolates examined for beta-lactamase production by employing nitrocefin. Data were analyzed using SPSS version 20 software and logistic regressions were applied to assess any association between dependent and independent variables. P values < 0.05 were taken as statistically significant. Results: Of the 378 swabs analyzed, <i>S. aureus</i> was recovered from 179 (47.4%). The prevalence of <i>S. aurues</i> was higher in females than males 95(53%) versus 84(47%). Out of 179 <i>S. aureus</i> isolates, 67(37.43%) were found out to be MRSA and the remaining 112(62.57%) were MSSA. <i>S. aureus</i> isolates were more resistant to penicillin 172(96.1%) and least resistant for vancomycin 10(5.6%) and cephalothin 9(5.0%). MRSA isolates were 67(100%) resistant for penicillin, 63(94.0%) for erythromycin, 62(92.5%) for trimethoprim-sulfamethoxazole and least resistant for cephalothin 9(13.4%) and vancomycin 10(15.0%). Among 179 <i>S. aureus</i> isolates, 145(81.0%) were beta-lactamase producers. Furthermore, of 67 MRSA isolates, 61(91.0%) and out of 112 MSSA strains 99(88.4%) were beta-lactamase producers. Conclusion: In this study <i>S. aureus</i> isolates exhibited very high degree of resistance to different antibiotics. The prevalence of MRSA was high and this should necessitate caution in prescription of antibiotics without proper indication. The isolates were also multidrug resistant to several combinations of the tested antibiotics. The emergence of vancomycin resistant <i>S. aureus</i> highlights the value of prudent prescribing of antibiotics and avoiding their irrational use.