Purpose: Rural residents are less likely to obtain optimal care for many serious conditions and have poorer health outcomes than those residing in more urban areas. We determined whether rural vs urban residence affected postdischarge medication persistence and 1 year outcomes after stroke. Methods: The Adherence eValuation After Ischemic Stroke-Longitudinal (AVAIL) study is a multicenter registry of stroke patients enrolled in 101 hospitals nationwide. Medications were recorded at hospital discharge and again after 3 and 12 months. Persistence was defined as continuation of prescribed discharge medications. Participants were categorized as living in rural or urban settings by cross-referencing home ZIP code with metropolitan statistical area (MSA) designation. Findings: Rural patients were younger, more likely to be white, married, smokers, and less likely to be college graduates. There was no difference in stroke type or working status compared to urban patients, and there were minor differences in comorbid conditions. There were no differences based on rural vs urban residence in medication persistence at 3 or 12 months postdischarge and no differences in outcomes of recurrent stroke or rehospitalization at 12 months. Conclusion: Despite differences in patient characteristics, there was no difference in medication persistence or outcomes between rural and urban dwellers after hospitalization for ischemic stroke or transient ischemic attack (TIA).