BACKGROUND: In theory, active surveillance of methicillin-resistant Staphylococcus aureus (MRSA) reduces MRSA spread by identifying all MRSA-colonized patients and placing them under contact precautions. In October 2007, Illinois mandated active MRSA surveillance in all intensive care units, including neonatal intensive care units (NICUs) and pediatric intensive care units (PICUs). We evaluated MRSA trends in a large metropolitan region in the wake of this law. METHODS: Chicago hospitals with a NICU or PICU were recruited for 8 single-day point prevalence surveys that occurred twice-yearly between June 2008 and July 2011 and then yearly in 2012 to 2013. Samples from all patients were cultured for MRSA (nose and umbilicus for neonates, nose and groin for pediatric patients). Hospital-reported admission MRSA-screening results also were obtained. Point prevalence cultures were screened for MRSA by using broth enrichment, chromogenic agar, and standard confirmatory methods. RESULTS: All eligible hospitals (N = 10) participated (10 NICUs, 6 PICUs). Hospital-reported adherence to state-mandated MRSA screening at admission was high (95% for NICUs, 94% for PICUs). From serial point prevalence surveys, overall MRSA prevalences in the NICUs and PICUs were 4.2% (89 of 2101) and 5.7% (36 of 632), respectively. MRSA colonization prevalences were unchanged in the NICUs (year-over-year risk ratio [RR], 0.93 [95% confidence interval (CI), 0.78-1.12]; P = .45) and trended toward an increase in the PICUs (RR, 1.25 [95% CI, 0.72-2.12]; P = .053). We estimated that 81% and 40% of MRSA-positive patients in the NICUs and PICUs, respectively, had newly acquired MRSA. CONCLUSIONS: In a region with mandated active MRSA surveillance, we found ongoing unchanged rates of MRSA colonization and acquisition among NICU and PICU patients.