In order to determine the comparative efficacy of vancomycin, teicoplanin, levofloxacin, moxifloxacin, and linezolid against methicillin- and ciprofloxacin-resistant Staphylococcus aureus, each agent was tested against 65 genetically different strains using the microbroth dilution method. All of the isolates were typed using the enterobacterial repetitive intergenic consensus polymerase chain reaction to exclude multiple isolates of epidemic clones. Susceptibility testing revealed that all of the isolates were susceptible to vancomycin and teicoplanin. Linezolid exhibited minimum inhibitory concentration (MIC) levels ranging from 1 to 4 mg/l (MIC90, 4 mg/l). The MICs of moxifloxacin and levofloxacin ranged from 0.01 to 8 mg/l (MIC90, 8 mg/l) and 0.25 to 32 mg/l (MIC90, 16 mg/l), respectively. Thus, linezolid is active against methicillin- and ciprofloxacin-resistant Staphylococcus aureus, whereas moxifloxacin may need to be administered at a dose higher than recommended in order to successfully treat serious infections.