Thirty-eight orthopedic patients with proven methicillin-resistant Staphylococcus aureus (MRSA) infections were assessed as to the effectiveness of treatment. All patients were admitted between June 1981 and September 1983 and were among the 508 patients who had positive cultures for MRSA during that period. The average age of the patients was 32.5 years. Thirty-two patients had fractures. In 70% of the patients the injury was due to a motor vehicle accident. Sixty percent of the patients had Grade III open fractures with severe soft tissue injury or associated vascular injury. All patients were given antibiotics within 30 days of a positive culture, with 97% getting a first-generation cephalosporin. There were an average of 5.5 surgical procedures per patient (range, one to 16). Nine patients (24%) required amputation and eight (21%) lost joints either by excision or fusion. Only 14 patients (37%) healed without drainage. Four patients (10%) healed the original fracture or surgery with chronic drainage. There were three nonunions, two of which continue to drain. The antibiotic cost for Vancomycin alone increased 300%, from $2,000 in 1982 to approximately $680,000 in 1983. Methicillin-resistant in 1983. Methicillin-resistant S. aureus (MRSA) has significant epidemic potential. Infection with this organism carries a high-morbidity in order to control the organism. Any reported case of MRSA should be isolated quickly and thoroughly investigated epidemiologically in an attempt to prevent an epidemic. Vancomycin is the antibiotic of choice. Emphasis should be placed on the interruption of transmission of MRSA within and among hospitals. Serious consideration must be given to the long-term effects of prophylactic antibiotics.