BACKGROUND: States, including Illinois, have passed legislation mandating the use of International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes for reporting healthcare-associated infections, such as methicillin-resistant Staphylococcus aureus (MRSA). OBJECTIVE: To evaluate the sensitivity of ICD-9-CM code combinations for detection of MRSA infection and to understand implications for reporting. METHODS: We reviewed discharge and microbiology databases from July through August of 2005, 2006, and 2007 for ICD-9-CM codes or microbiology results suggesting MRSA infection at a tertiary care hospital near Chicago, Illinois. Medical records were reviewed to confirm MRSA infection. Time from admission to first positive MRSA culture result was evaluated to identify hospital-onset MRSA (HO-MRSA) infections. The sensitivity of MRSA code combinations for detecting confirmed MRSA infections was calculated using all codes present in the discharge record (up to 15); the effect of reviewing only 9 diagnosis codes, the number reported to the Centers for Medicare and Medicaid Services, was also evaluated. The sensitivity of the combination of diagnosis codes for detection of HO-MRSA infections was compared with that for community-onset MRSA (CO-MRSA) infections. RESULTS: We identified 571 potential MRSA infections with the use of screening criteria; 403 (71%) were confirmed MRSA infections, of which 61 (15%) were classified as HO-MRSA. The sensitivity of MRSA code combinations was 59% for all confirmed MRSA infections when 15 diagnoses were reviewed compared with 31% if only 9 diagnoses were reviewed ([Formula: see text]). The sensitivity of code combinations was 33% for HO-MRSA infections compared with 62% for CO-MRSA infections ([Formula: see text]). CONCLUSIONS: Limiting analysis to 9 diagnosis codes resulted in low sensitivity. Furthermore, code combinations were better at revealing CO-MRSA infections than HO-MRSA infections. These limitations could compromise the validity of ICD-9-CM codes for interfacility comparisons and for reporting of healthcare-associated MRSA infections.