Antimicrobial susceptibility patterns, Panton-Valentine leukocidin (PVL) occurrence, and staphylococcal cassette chromosome mec (SCCmec) types in methicillin-resistant Staphylococcus aureus (MRSA) strains isolated from children and adults at Vanderbilt University Medical Center during a 12-month period were evaluated. A total of 1,315 MRSA isolates were collected, of which 748 (36.7%) were recovered from children. Among all isolates, 448 (34.1%) were SCCmec-II, and 847 (64.4%) were SCCmec-IV. More SCCmec-IV isolates were recovered from children than SCCmec-II isolates (424 [50.1%] versus 50 [11.2%]; odds ration [OR]=7.98; P<0.000001). The PVL gene was detected in 93.6% of SCCmec-IV isolates, in contrast to 0.2% in SCCmec-II isolates. Within SCCmec-IV isolates, a statistically higher PVL occurrence was noticed in children (98.1%) than in adults (89.1%) (OR=6.34; P<0.000001). Overall, SCCmec-II strains showed greater resistance than SCCmec-IV strains to clindamycin, erythromycin, levofloxacin, gentamicin, rifampin, minocycline, and trimethoprim-sulfamethoxazole. Both SCCmec-II and SCCmec-IV strains recovered from adults were more resistant to these antibiotics than those recovered from children. SCCmec-II strains were predominantly recovered from the respiratory tract, whereas SCCmec-IV strains were predominantly recovered from skin, soft tissue, abscesses, and surgical wounds. These data indicate that SCCmec-IV MRSA isolates frequently infect children in middle Tennessee and are likely to harbor the PVL gene.