Mediastinitis caused by MRSA (Methicillin-Resistant Staphylococcus aureus) remains an intractable infection producing high mortality even in these days of advanced chemotherapy. The authors report a case of mediastinitis due to MRSA complicated with acute renal failure following mitral valve replacement. The patient's mediastinum had been thoroughly cleaned with physiological saline solution with 0.2% povidone iodine, and underwent a chemotherapy regimen of mini-dose vancomycin. The patient made favorable progress and recovered completely. Our patient's progress confirmed that when chemotherapy using vancomycin is administered in a patient whose condition is complicated with acute renal failure, closely monitoring the vancomycin serum concentration is essential. Intermittent mini-dose intravenous administration is sufficient to maintain an effective vancomycin serum concentration. In our case, vancomycin serum concentration measured before and at completion of dialysis revealed no appreciable decline.