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Methicillin-resistant Staphylococcus aureus (MRSA) has become a main clinical and epidemiological concern for the past decades. These isolates have spread worldwide, causing health care– and community-associated infections. The aim of the present work was the determination of antibiotic resistance profile and simultaneous detection of psm-α and sasX genes in the clinical MRSA strains isolated from Tehran—the first report from Iran.This descriptive study was performed on hospitalized patients during August to February 2015. Antibiotic susceptibility test for all S. aureus isolates was conducted on Mueller-Hinton agar. The presence of mecA, sasX, and psm genes was detected by multiplex polymerase chain reaction method.Of 153 S. aureus, 79 (51.6%) of the strains carried the mecA gene. Molecular analysis of mecA-positive S. aureus showed that the prevalence of sasX and psm genes was 13.9% (11/79) and 7.6% (6/79), respectively.This is the first report of sasX and psm genes among S. aureus isolates from Iran. Phenol-soluble modulins have recently appeared as a novel toxin family describing the virulence potential of vastly aggressive S. aureus. Current understanding is needed on S. aureus surface protein-encoding gene sasX, which plays a vital role in colonization and pathogenesis of MRSA.