Staphylococcus aureus is one of the most common community and nosocomial pathogens and it mainly causes skin and soft tissue infections. So the current study aimed to study the prevalence of VRSA strains in Zagazig University Hospitals. study their antibiotic susceptibility profile and therapy to control and present the transmission of VRSA strains among the health care settings. One hundred pus samples were collected from post operation wounds of a study group of inpatients in Zagazig University-Hospital. Bacteria colonizing the wounds were isolated on specific culture media thereafter purified and divided into 4 groups depending on their morphological characters and Gram's stain reaction. Isolated bacteria were divided into 4 groups. Group (I) represented 38% of total isolates; while group (II) & (III) represented 20% and group (IV) 22%. Isolated bacteria related to groups I, II, III & IV were preliminary identified as S. aureus. E. coli, K. pneumoniae and P. aeruginosa, respectively. Antibiotic susceptibility of the 4 groups of isolated bacteria against 15 different antibiotics revealed that imipinem and vancomycin are the most effective antibiotics against S. aureus group with sensitivity 86.9% and 84.2%, respectively; meanwhile, Imipenem showed highest activity (100%) against E. coli and K. pneumoniae and 86.3% in case of P. aeruginosa. Depending on antibiotic susceptibility pattern some strains were selected as multi-resistant isolates. Strains encoded S. aureus 6 & 16 were resistant to 11 antibiotics out of 15 (73.3%) and 10 antibiotics out of 15 (66.7%), respectively. the two mentioned strains are methicillin and vancomycin resistant, thus suspected as MRS A and VRSA strains. Imipenem antibiotic as the most effective antibiotic was tested for its MIC and MBC against the selected multi-resistant isolates of the 4 bacterial groups. MICs and MBCs of S. aureus 6 & I6 were (62.5 & 31.25) μg/ml and(62.5 & 62.5) μg/ml, respectively. Amplification of 16S rRNA gene of selected multi-resistant strains S. aureus (6 & 16) revealed the occurrence of amplicons with molecular size 1500bp for both strains. The target van A gene was amplified using Polymerase chain reaction (PCR) in which the primers F: EAl & R: EA2 gave rise to a fragment of about 800 bp size in both tested strains. In conclusion The control of emergence and spread of antimicrobial resistance among the most common human bacterial pathogens is probably one of the most important challenges for the scientific and medical community. This emergence was significantly marked in hospitals that had been endemic with (MRSA) strains and followed the policy of empirical use of glycopeptides. Vancomycin being the cornerstone of treatment of patients with serious MRSA infections for some decades has exerted considerable selection pressure on S. aureus strains in the healthcare setting.