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Background: The clinical utility of methicillin-resistant Staphylococcus aureus (MRSA) nasal screening appears promising for antimicrobial stewardship programs. However, a paucity of data remains on the diagnostic performance of culture-based MRSA screen in the intensive care unit (ICU) for pneumonia and bacteremia. Objective: The objective of this study was to compare the predictive value of culture-based MRSA nasal screening for pneumonia and bacteremia in ICU and general ward patients. Methods: This multicenter, retrospective study was conducted over a 23-month period. Adult patients with MRSA nasal screening ≤48 hours of collecting a respiratory and/or blood culture with concurrent initiation of anti-MRSA therapy were included. The primary endpoint was to compare the negative predictive value (NPV) associated with culture-based MRSA nasal screening between ICU and general ward patients with suspected pneumonia. Results: A total of 5106 patients representing the ICU (n = 2515) and general ward (n = 2591) were evaluated. The NPV of the MRSA nares for suspected pneumonia was not significantly different between ICU and general ward patient populations (98.3% and 97.6%, respectively; P = 0.41). The MRSA nares screening tool also had a high NPV for suspected bacteremia in ICU (99.8%) and general ward groups (99.7%) ( P = 0.56). The overall positive MRSA nares rates in the ICU and general ward patient populations were 9.1% and 8.2%, respectively ( P = 0.283). Moreover, MRSA-positive respiratory and blood cultures among ICU patients were 5.8% and 0.8%, respectively. Conclusion and Relevance: Our findings support the routine use of MRSA nasal screening using the culture-based method in ICU patients with pneumonia. Further research on the clinical performance for MRSA bacteremia in the ICU is warranted.