Although oxacillin-resistant Staphylococcus aureus (ORSA) are well-established pathogens in many hospitals, the impact of infection control measures on the clonal distribution of ORSA is poorly defined. A citywide surveillance study of Staphylococcus aureus in Brooklyn, New York revealed that 36% of isolates were ORSA. Molecular typing showed that one strain (Cluster A) accounted for more than half of the isolates and was present in all 15 hospitals. In one hospital, a distinct strain (Cluster B) accounted for 20% of ORSA isolates. Infection control measures in this hospital significantly decreased the percentage of clinical isolates that belonged to Cluster B, but did not have an effect on the strain endemic to the city (Cluster A). Regional infection control strategies may need to be developed to limit the spread of the ORSA clone endemic to this area.