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Background We aimed to examine the clinical value of serial MRSA surveillance cultures to rule out a MRSA diagnosis on subsequent cultures during a patient's surgical intensive care unit (SICU) admission. Material and Methods We performed a retrospective cohort study to evaluate patients who received a MRSA surveillance culture at admission to the SICU (n = 6,915) and collected and assessed all patient cultures for MRSA positivity during their admission. The primary objective was to evaluate the transition from a MRSA negative surveillance on admission to MRSA positive on any subsequent culture during a patient's SICU stay. Percent of MRSA positive cultures by type following MRSA negative surveillance cultures was further analyzed. Measurements and Main Results 6,303 patients received MRSA nasal surveillance cultures at admission with 21,597 clinical cultures and 7,269 MRSA surveillance cultures. Of the 6,163 patients with an initial negative, 53 patients (0.87%) transitioned to MRSA positive. Of the 139 patients with an initial positive, 30 (21.6%) had subsequent MRSA positive cultures. Individuals who had an initial MRSA surveillance positive status on admission predicted MRSA positivity rates for cultures in qualitative lower respiratory cultures (64.3% versus. 3.1%), superficial wound (60.0% versus 1.6%), deep wound (39.0% versus 0.8%), tissue culture (26.3% versus 0.6%), and body fluid (20.8% versus 0.7%) cultures when compared to MRSA negative patients on admission. Conclusion Following MRSA negative nasal surveillance cultures patients showed low likelihood of MRSA infection suggesting empiric anti-MRSA treatment is unnecessary for specific patient populations. SICU patient's MRSA status at admission should guide empiric anti-MRSA therapy.