In response to epidemic methicillin-resistant Staphylococcus aureus (MRSA) in the community, the Illinois General Assembly mandated that all patients admitted to intensive care units statewide be screened for MRSA. Screening was instituted at our neonatal intensive care unit (NICU) in September 2007 by a polymerase chain reaction (PCR)-based strategy. The law created an opportunity to determine the rate of MRSA colonization among neonates, to gather information about subsequent MRSA infections, and to evaluate risk factors for MRSA colonization on admission to the NICU.