To investigate the association of both tsst-1 and pvl with mecA genes in clinical Staphylococcus aureus (S. aureus) strains obtained from a tertiary care hospital, Mansoura-Egypt. Besides, relating these genes to antibiotic resistance patterns in such isolates. A prospective study was performed over clinical samples obtained from patients showing evidence of infection at Mansoura University Children Hospital, Egypt. Staphylococcus aureus isolates were obtained to test their antibiotic sensitivity pattern by disk diffusion method, E-test strips besides oxacillin agar screen test followed by screening such isolates for mecA, pvl and tsst-1 genes by polymerase chain reaction. Out of 180 isolated S. aureus strains, 88 isolates (48.9%) were methicillin resistant. The tsst-1 gene was positive in 65.9% of methicillin resistant S. aureus (MRSA) and 55.4% of methicillin sensitive S. aureus (MSSA) strains. Carriage of mecA and tsst-1 genes was not significantly associated (P=0.69). The pvl gene was positive in 23.9% of MRSA and 9.8% of MSSA isolates showing a significant association with mecA gene (P=0.04*). The mecA gene was significantly associated with multidrug resistant isolates (p= 0.041*). There was no significant association between antibiotic resistance and the presence of tsst-1 or pvl genes. The tsst-1 gene had a high prevalence among S. aureus isolates and it was similarly distributed in both MRSA and MSSA groups. The pvl gene was significantly associated with MRSA group. Antibiotic resistance pattern of S. aureus was not significantly associated to the presence of tsst-1 or pvl genes in any way.