Staphylococcus aureus (S. aureus) is one of the most important pathogens involved in food borne infections from consumption of milk and dairy products. Antibiotics are used to treat livestock commonly, resulting in a problem of antibiotic resistance of Staphylococcus aureus which has a huge risk for public health all over the world. Because of its toxin-mediated pathogenicity, antibiotic resistance, and invasion, Staphylococcus aureus consider one of the most significant pathogens. The present study was performed on a total of 150 raw cow^'s milkfrom different sources at Damietta Governorate. The examined samples were taken in ice box within an hour for bacteriological examination. The results revealed that 48 out of 150 isolates (32 %) were positive for S. aureus. Out of those 48 isolates, 25 (52.08%) were coagulase positive and the other 23 (47.92%) were coagulase negative. Detection of antibiotic sensitivity of S. aureus isolates by disk diffusion method and confirmed by viteck2 compact method revealed that against 10 antimicrobial discs S. aureus show resistance against penicillin G, oxacillin and tetracycline antibiotics by 24% followed by 16% resistance against ciprofloxacin and show good sensitivity against amikacin, chloramphenicol and erythromycin antibiotics. These results obtained according to CLSI (2016). This study aimed to isolate and identify the multi drug resistant coagulase positive S. aureus from raw cow^'s milk at different regions of Damietta governorate and evaluate its antimicrobial activity against different groups of antibiotics.