Introduction/Hypothesis: Stroke remains a significant public health concern. North Carolina (NC) has the 11 th highest stroke mortality in the United States and an increasingly diverse population with respect to rurality and race-ethnicity. We assessed the hypothesis that rural stroke patients have higher in-hospital mortality than urban stroke patients in NC. We also explored the interaction between rurality and race-ethnicity on stroke mortality. Methods: We conducted a retrospective study of stroke hospitalizations at 115 NC hospitals from January 2019-September 2020. Data were obtained from an inpatient database of patient demographics, county of residence, insurance, admission date, and discharge disposition and diagnoses. Eligible patients included adults with principal discharge diagnosis codes for stroke (ICD-10-CM I60.xx-I63.xx) and were classified by rurality defined by the NC Office of Rural Health. Multivariable logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) comparing in-hospital mortality in rural versus urban patients, overall and stratified by race-ethnicity subgroups. Results: Among 32,808 patients, 37% resided in rural counties. Patients were mean 69 years old, 50% female, 30% Black, and 3% Hispanic. Unadjusted in-hospital mortality was lower in rural versus urban patients (4.2% and 5.0%, respectively). Adjusted model found a weak, non-significant association between rurality and stroke mortality (OR 1.06, 95% CI 0.95-1.19; Table 1). In race-ethnicity subgroups, rural-urban ORs were not statistically significant although the point estimates suggest modestly greater differences among racial/ethnic minorities compared to White patients. Conclusions: We found minimal, adjusted rural-urban differences in in-hospital stroke mortality in NC statewide and within race-ethnicity subgroups. Further research is needed to investigate potential disparities in long-term stroke mortality and morbidity and their underlying determinants.