Background: Vancomycin is one of the main therapies for methicillin-resistant S. aureus (MRSA), however emergence of resistant strains is rising. Nanoparticles can offer promising solution. So, we studied the effect of gold nanoparticles (AuNPs) in enhancing vancomycin potential against MRSA clinical isolates from different types of infections. Methods: The susceptibility patterns of vancomycin, AuNPs, and vancomycin-conjugated gold nanoparticles (V-AuNPs) were evaluated on 30 MRSA isolates obtained from various clinical samples by using the microtiter broth dilution method. AuNPs and V-AuNPs were prepared by using a straightforward technique of microwave-assisted synthesis. Results: Twenty-seven (90%) MRSA isolates were susceptible to vancomycin and three (10%) showed intermediate susceptibility, with mean minimum inhibitory concentration (MIC) 2.68 ± 2.07 μg /ml, inhibitory concentration (conc.) to 50% of MRSA (IC50) 1.95 μg /ml and inhibitory conc. to 90% of the isolates (IC90) 3.9 μg /ml. While the synthesized AuNPs demonstrated a bactericidal effect on all the tested isolates with mean MIC 164.6 ± 62.5 μg /ml, IC50 125 μg /ml, and IC90 250 μg /ml. Meanwhile, V-AuNPs demonstrated synergistic bactericidal effect on all thirty (100%) tested MRSA isolates with mean MIC 0.40 ± 0.46 μg /ml, IC50 0.24 μg /ml, and IC 90 0.48 μg /ml.  Moreover, V-AuNPs demonstrated minimal cytotoxic concentration up to 100 and 98.65 percent viability on human foreskin fibroblast (HFF-1) cell line at conc. of 2 μg/ml and 3.9 μg/ml respectively. Conclusions: The V-AuNPs display superior antibacterial activity as compared to vancomycin and AuNPs alone as a potentially effective therapy against MRSA.