PROJECT SUMMARY/ABSTRACT In the United States (US), ischemic stroke is a serious life-threatening condition that affects more than 691,650 people and results in 121,800 deaths annually. Stroke incidence is expected to rise by more than 200% within the next 30 years as the country’s population rapidly ages, placing increased strain on already overextended hospitals and pushing yearly US stroke-related expenses upwards of $34 billion. Stroke burden in the US is further complicated by distinct regional and state differences in stroke incidence and mortality rates. Several US studies suggest that exposure to common air pollutants, including CO, NO2, O3, PM2.5, and SO2, may be contributing to these differences, but findings have been inconsistent. Moreover, the lack of a national stroke surveillance system has created a gap in current US research on associations between air pollution and stroke across the country. We propose to fill this research gap by studying the associations of short- and long-term exposure to air pollution (CO, NO2, O3, PM2.5, and SO2) with ischemic stroke hospitalization and 30-day all- cause readmission following ischemic stroke in elderly fee-for-service Medicare beneficiaries. The study will examine patterns at the regional and state levels to identify potential variation in the associations by geographic location. To accomplish the study goals, we will link national Medicare fee-for-service beneficiary data from 2014-2015 with publicly available Environmental Protection Agency air pollution data. Specifically, the study aims are: 1) to determine national-, regional-, and state-level associations between short-term CO, NO2, O3, PM2.5, and SO2 exposure and ischemic stroke hospitalization in the US; 2) to examine associations between short-term CO, NO2, O3, PM2.5, and SO2 exposure and 30-day all-cause hospital readmission nationwide by geographic region and state; and 3) to ascertain associations between long-term CO, NO2, O3, PM2.5, and SO2 exposure with ischemic stroke hospitalization in the US at the national, regional, and state levels. This work will provide important insights about the potential associations between common environmental factors and ischemic stroke hospitalizations and post-discharge outcomes for elderly fee-for- service Medicare beneficiaries as well as provide insights about geographic patterns of exposure and stroke risk across the US. The study results will address important gaps in our understanding of the associations between air pollutants and stroke risk; information that has the potential to identify additional environmental risk factors for stroke for our aging society.