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Methicillin-resistant S. aureus (MRSA) and their antimicrobial resistance pose exacerbating global health threats and endangering everyone. Thus, the prevalence, molecular characterization of virulence genes, and antimicrobial resistance patterns of strains isolated from 225 beef burger and hot dog sandwiches vended in Mansoura city, Egypt were determined. 83.1% of the sandwiches tested were contaminated with coagulase-positive S. aureus, with a mean count of 4 × 10 3  CFU/g. Genes encoding mecA, α-hemolysin, staphylococcal enterotoxins, and toxic shock syndrome toxin-1 were detected in 22.6%, 96.3%, 61.1%, and 0% of the strains isolated, respectively. Of the 190 coagulase-positive strains, 43 (22.6%) were confirmed as MRSA. Among them, 4 strains (2.1%) were vancomycin-resistant S. aureus (VRSA) and resistant to all antimicrobials tested. Interestingly, all isolates were resistant to at least one of the antimicrobials tested, with 75.2% being multi-drug resistant (MDR) and an average multiple antimicrobial resistance (MAR) index of 0.503. Not less important, 100%, 96.3%, 90.5%, 79.5%, 73.7%, 62.6%, and 48.9% of isolates were resistant to Kanamycin, Nalidixic acid, Cefotaxime, Sulphamethoxazole-Trimethoprim, Penicillin G, Tetracycline, and Cephalothin, respectively. The potential hazard of MDR-, MRSA-, and VRSA-contaminated sandwiches may be an indication of the presence of what is more dangerous. Hence, strict hygienic measures and good standards of food handler's personal hygiene to prevent transmission of these pathogens to consumers are imperative., (Copyright © 2021 Elsevier B.V. All rights reserved.)