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Introduction: Little is known about stroke incidence, mortality and risk factor prevalence in rural versus urban regions. We used linked population-based administrative databases to compare cardiovascular risk factors, stroke incidence and stroke-related death in residents of rural and urban Ontario, Canada.Methods: We used a sub-population of the Cardiovascular Health in Ambulatory Care Research Team (CANHEART) cohort, consisting of individuals aged 40 to 105 in Ontario with no known hospitalization for stroke in the 20 years prior to January 1, 2008. We defined rural regions as those with a population size ≤ 30, 000. We compared the age- and sex- standardized prevalence of risk factors, as well as 5-year stroke incidence and stroke-related mortality rates, in people residing in rural versus urban areas.Results: The study sample consisted of 6,207,032 individuals. Compared to residents of urban regions, rural residents were more likely to smoke (25.3% versus 19.3%), be obese (25.1% versus 19.3%) and live in a low-income area (43.5% versus 38.3%) (P<0.001 for all comparisons). However, there were no differences in the proportion of residents with hypertension, diabetes and atrial fibrillation. Age- and sex-standardized stroke incidence was higher in rural compared to urban areas (2.18 versus 1.99 events/1000 person-years; p<0.001), as was stroke-related mortality (0.79 versus 0.65 events/1000 person-years; p<0.001).Conclusions: Certain cardiovascular risk factors have increased prevalence in rural areas compared to urban areas. Furthermore, stroke incidence and mortality rates were greater in rural areas in Ontario. Future efforts should focus on reducing regional discrepancies in social determinants of health and addressing risk factor prevalence, particularly smoking and obesity, in rural regions.