Background/aim: Panton-Valentine leukocidin (PVL)-positive methicillin-resistant Staphylococcus aureus (MRSA) infections are increasing in some regions of Iran. The aim of the current study was to assess the epidemiology and molecular characteristics of S. aureus isolated from patients with skin infections in Shiraz, Iran. Materials and methods: Swab samples were obtained from patients admitted to the skin and burn units of hospitals. The medical records of each patient were collected via questionnaire. All staphylococcal isolates were collected and examined by conventional methods for detecting S. aureus strains. PCR was used to detect S. aureus harboring the mecA and pvl genes. Results: Out of 243 staphylococcal isolates, 55 (22.6%) S. aureus and 91 (37.4%) S. epidermidis were detected. Of the 45 patients, 21 (46.7%) were S. aureus carriers. The mecA gene was identified in 60% of S. aureus isolates, and the rest were sensitive to methicillin. Of the S. aureus isolates, 54.5% were positive for the pvl gene. Conclusion: This study revealed a high prevalence of PVL-positive MRSA strains in the evaluated hospitals. Thus, early diagnosis of infections caused by this pathogen seems to be necessary by intake screening allowing for proper treatment, especially in high-risk patients and in order to prevent the spread of infection.