Background:The uncontrolled use of vancomycin led to an upsurge of vancomycinresistant S. aureus (VRSA) throughout the world. Objective: The goal of this study is to screen vancomycin resistance among MRSA isolates, determine antimicrobial resistance pattern and evaluate the distribution of virulence genes among these isolates. Methodology: A total of 127 S. aureus clinical isolates were used, MRSA isolates were identified and antimicrobial sensitivity pattern for nine antimicrobial agents from different classes was assessed. In addition, vancomycin MIC was determined by standard agar dilution method and PCR identification of vancomycin resistance encoding genes vanA and vanB was performed. Moreover, the prevalence of eight different virulence genes was determined among different vancomycin resistance categories. Results: All isolates were identified phenotypically as MRSA. However, mecA gene was detected only in 95.28% of isolates. The highest and lowest percentage of resistance was recorded for clindamycin (82.68%) and trimethoprim (11.81%), respectively. Vancomycin resistance level was 23.62% of isolates, while vanA and vanB genes were detected only in 16.67% and 10% of VRSA isolates, respectively. The highest prevalence of virulence genes was found for icaA, followed by hld, hlb, icaD, hlg, hla, tsst and cna, respectively in the tested isolates. In addition, VRSA isolates showed higher mean virulence score (MVS) of 3.6 compared to VISA and VSSA isolates. Conclusion: This study highlights the alarming problem of the increasing incidence of VRSA infections in Egypt. Therefore, there is an urgent need to rationalize vancomycin consumption and to continuously monitor the prevalence of VRSA strains.