ABSTRACT The goal of this highly interdisciplinary project, which draws on epidemiological, hydrological, and biostatistical expertise, is to use spatial data linkage to connect drinking water arsenic data (or model predictions) to cardiometabolic health outcomes in the REasons for Geographic And Racial Differences in Stroke (REGARDS) Study. The REGARDS Study is a biracial (African American and white) cohort with participants recruited from across the United States, with emphasis on the Southeastern United States. The large sample size and geographic variation in this cohort make it an ideal resource for spatial drinking water arsenic epidemiology. This proposed work will support the development and refinement of a novel data analytic pipeline, which will allow integration of multiple data streams (community water system public supply water quality data, and groundwater predictions relevant for private wells) to give epidemiological inferences about drinking water arsenic and cardiometabolic health outcomes. The primary outcomes of the study are blood pressure at the REGARDS Study baseline visit, hypertension prevalence at the REGARDS Study baseline visit, and incident ischemic stroke among participants in the REGARDS Study at risk of incident ischemic stroke at baseline. The study will consider potential differences in response to arsenic according to putative effect modifiers (e.g., sex, race). Successful completion of the project aims will not only address significant knowledge gaps about drinking water arsenic’s potential salience to cardiometabolic health in the United States, but also provide a highly innovative data analysis pipeline that can be the foundation for future drinking water health research in the United States.