Background: Many hospitals screen patients for methicillin-resistant Staphylococcus aureus (MRSA) on admission to the intensive care unit (ICU). We hypothesized that this screening information could be used to assist with empiric antibiotic decisions. Methods: The medical records of patients admitted to a university-affiliated community hospital as well as a tertiary-care university hospital were reviewed. Patients admitted to the ICU were screened for MRSA colonization with a nasal swab that was analyzed with either chromogenic medium (hospital 1) or polymerase chain reaction (PCR) (hospital 2). The results of the nasal swab were compared with clinical culture results. Results: There were 141 patients, and 167 cultures were obtained. The majority of the cultures (70%) were performed on sputum specimens in an effort to diagnose pneumonia. The remaining cultures were performed on blood (10.1%), incisions (21.5%), and urine (3.4%). The overall sensitivity of nasal swab results was 69.5%. However, the sensitivity was significantly higher for nasal swab screening performed within six days of clinical cultures compared with screening performed seven days or more before cultures were obtained. (79% vs. 46%; p < 0.0001). Sensitivity also differed significantly depending on the surveillance method, being significantly higher among patients screened with PCR within six days of developing an infection than in patients screened with chromogenic medium (88% vs. 65.5%; p = 0.006). Conclusion: Screening with PCR analysis of nasal swab specimens is a highly sensitive test for MRSA in clinical cultures. Clinicians may be able to use the swab results to tailor more appropriate empiric antimicrobial regimens. The results with chromogenic medium screening are markedly poorer, which suggests that clinicians should view them with caution.