Most invasive methicillin-resistant Staphylococcus aureus (iMRSA) infections have onset in the community but are associated with healthcare exposures. More than 25% of cases with healthcare exposure occur in nursing homes (NHs) where facility-specific iMRSA rates vary widely. We assessed associations between nursing home characteristics and iMRSA incidence rates to help target prevention efforts in NHs. Methods: We used active, laboratory- and population-based surveillance data collected through the Emerging Infections Program during 2011–2015 from 25 counties in 7 states. NH-onset cases were defined as isolation of MRSA from a normally sterile site in a surveillance area resident who was in a NH within 3 days before the index culture. We calculated MRSA incidence (cases per NH resident day) using Centers for Medicare & Medicaid Services (CMS) skilled nursing facility cost reports and described variation in iMRSA incidence by NH. We used Poisson regression with backward selection, assessing variables for collinearity, to estimate adjusted rate ratios (aRRs) for NH characteristics (obtained from the CMS minimum dataset) associated with iMRSA rates. Results: Of 590 surveillance area NHs included in analysis, 89 (15%) had no NH-onset iMRSA infections. Rates ranged from 0 to 23.4 infections per 100,000 resident days. Increased rate of NH-onset iMRSA infection occurred with increased percentage of residents in short stay ≤30 days (aRR, 1.09), exhibiting wounds or infection (surgical wound [aRR, 1.08]; vascular ulcer/foot infection [aRR, 1.09]; multidrug-resistant organism infection [aRR, 1.13]; receipt of antibiotics [aRR, 1.06]), using medical devices or invasive support (ostomy [aRR, 1.07]; dialysis [aRR, 1.07]; ventilator support [aRR, 1.17]), carrying neurologic diagnoses (cerebral palsy [aRR, 1.14]; brain injury [aRR, 1.1]), and demonstrating debility (requiring considerable assistance with bed mobility [aRR, 1.05]) (Table). iMRSA rates decreased with increased percentage of residents receiving influenza vaccination (aRR, 0.96) and with the presence of any patients in isolation for any active infection (aRR, 0.83). Conclusions: iMRSA incidence varies greatly across nursing homes, with many NH patient and facility characteristics associated with NH-onset iMRSA rate differences. Some associations (short stay, wounds and infection, medical device use and invasive support) suggest that targeted interventions utilizing known strategies to decrease transmission may help to reduce infection rates, while others (neurologic diagnoses, influenza vaccination, presence of patients in isolation) require further exploration to determine their role. These findings can help identify NHs in other areas more likely to have higher rates of NH-onset iMRSA who could benefit from interventions to reduce infection rates.