Background: Staphylococcus aureus is frequently implicated in healthcare-associated infections in the United States, and a substantial proportion of these infections are attributed to methicillin-resistant Staphylococcus aureus (MRSA). Although MRSA infections have decreased in health care settings, accurate estimates of the rate of decline call for risk-adjusted methods for calculating the resistant proportion (%R), that is, the proportion of S. aureus resistant to cefoxitin or oxacillin. Risk-adjusted %R also enables more accurate interhospital comparisons and can serve as a quantitative guide and evaluation metric for prevention efforts. Methods: To develop a risk-adjusted %R for S. aureus, we analyzed the antimicrobial susceptibility test (AST) results for S. aureus isolates reported to the CDC NHSN Antimicrobial Resistance Option during 2017–2018. Isolates were reported for cerebrospinal fluid (CSF), blood, lower respiratory tract (LRT), and urine. Isolates without cefoxitin and oxacillin test results, or from the facilities that had >10% missing test results were excluded. Test results were differentiated between those associated with community-onset and hospital-onset (HO) infections by defining the latter group as test results for isolates obtained 3 days or more after hospital admission. Logistic regression was used to evaluate the factors associated with oxacillin/cefoxitin resistance. Hospital, patient and isolate-level variables from NHSN annual survey and AR option were assessed as covariates. Variable entry into the models is based on significance level P < .05. Results: Among 9,992 hospital-onset SA isolates from 9,019 patients in 315 facilities, 5,488 (54.9%) were MRSA. Logistic regression showed that a higher proportion of HO-MRSA was significantly associated with older age, female, particular sources of specimen (urine and LRT), and selected hospital characteristics: hospitals not serving as major teaching hospitals, hospitals with a higher proportion of MRSA among community-onset SA isolates, hospitals with lower percentage of beds in intensive care units, and hospitals outsourcing AST service (Table 1). Conclusions: HO-MRSA is independently associated with community burden of MRSA, older and female patient populations, and hospital teaching status and AST practices, which highlights the importance of public health engagement and regional collaborations to prevent MRSA. To provide a standardized MRSA proportion for public health surveillance, taking some of these factors into account in MRSA proportion standardization should be considered.