In 2002, an increased incidence of nosocomial methicillin-resistant Staphylococcus aureus (MRSA) in our institution triggered a conventional investigation that failed to identify a common source. Molecular typing of the 70 nosocomial MRSA isolates obtained identified a predominant health care-associated clone A in the first trimester. Aggressive infection control measures led to a significant decrease in the number of isolates per 10,000 hospital days between the first trimester and the last 2 trimesters of 2003 (6.4 vs 3.8; P = .04). This was attributed to a decrease in clone A: SCCmec II, USA100, PVL gene-negative (2.3 per 10.000 patient-days vs 0.1 per 10,000 patient-days; P = .004). However, in 2003, 23% of the nosocomial isolates were SCCmec IV, USA300, PVL gene-positive. At that time, molecular methods allowed the detection and prevention of a nosocomial MRSA outbreak caused by a health care-associated clone; however, the community strains (SCCmec IV) have become a frequent cause of nosocomial infection in our institution.