Ocular infections caused by bacteria and their complications represent an important public health problem worldwide. The study was conducted to determine the antimicrobial resistance pattern and the emergence of cefoxitin- and vancomycin-resistant S. aureus causing ocular infections at El-Gharbia governorate hospitals. We collected 300 S. aureus causing ocular isolates from patients suffering from eye infections from four hospitals at El-Gharbia governorate, and the isolates were molecularly characterized using 23s rRNA PCR. Antibiotic sensitivity tests were performed using the disk diffusion test. A total of 90 (31%) S. aureus ocular isolates were identified, and distributed within the four hospitals as 25%, 33%, 48%, and 16% from Quotour hospital, El–Menshawy, El-Ramad and Quotour clinic, respectively. Moreover, S. aureus was isolated with 30.8 % and 31 % male and female patients. S. aureus ocular isolates were sensitive to ciprofloxacin, levofloxacin, cefuroxime, amikacin, azithromycin, norfloxacin, sulbactam/ampicillin and cefotaxime. In contrast, 89%, 90%, 100% and 85% of these isolates showed resistance to ampicillin, cefoxitin, doxycycline hydrochloride, and vancomycin. Whereas, the rest of S. aureus strains were cefoxitin- and vancomycin-intermediate resistant. This study alerts the emergence of cefoxitin- and vancomycin-resistant S. aureus causing ocular infections among hospitals in the El-Gharbia governorate. Additionally, ciprofloxacin is the most effective antibiotic against S. aureus causing ocular infections reported in this study.