A patient with infective endocarditis (IE) caused by methicillin-resistant Staphylococcus aureus (MRSA) was treated with vancomycin (VAN). VAN was ineffective, although therapeutic drug monitoring (TDM) indicated that the recommended trough level was maintained. Five MRSA isolates obtained at various times were analyzed to determine the minimum inhibitory concentration (MIC) and were subjected to population analysis, simulation analysis pulsed-field gel electrophoresis (PFGE). MRSA susceptible to VAN was isolated before and during the early stage of treatment, while an MRSA strain showing reduced VAN MIC was isolated during treatment. Simulation analysis indicated that the viable bacterial count only decreased to 10(-3) to 10(-4) cells after 72 h of incubation. The five MRSA strains isolated at various times were identical by PFGE.