Staphylococcus aureus is the predominant cause of bacteremia worldwide. We assessed the molecular epidemiology and antibiotic resistance of methicillin-resistant S aureus isolates causing bacteremia in southern Mississippi. Diverse genetic backgrounds in terms of staphylococcal cassette chromosome mec, pulsed-field gel electrophoresis, and multilocus sequence typing types of methicillin-resistant S aureus were identified as causing bacteremia in Mississippi. A strong association of Panton-Valentine leukocidin genes with elevated vancomycin minimum inhibitory concentration is one of the important findings of our study.