Abstract The concentration of tobacco retail stores in a specific area (i.e., tobacco retailer density) may produce or sustain higher smoking levels through increased exposure to tobacco marketing, access to cheaper tobacco products, and establishing tobacco use as a norm. Disparities in tobacco retailer density have been documented with African American, Latino, and low-income communities having higher tobacco retailer density than their counterparts. Some communities are exploring ways to reduce retailer density, but there is little empirical evidence about the potential impacts of such interventions. We propose to provide evidence regarding the impacts of retailer density on a) smoking behaviors; and b) subsequent health outcomes. In Aim 1 of this study we build a geocoded, longitudinal database of the approximately 275,000 tobacco retailers throughout the U.S. between 2000-2018. Using adaptive kernel density estimation, we will develop annual measures of census tract- and county- level tobacco retailer density and examine associations with area demographic characteristics. In Aim 2, we link the density data with county smoking data derived from the Behavioral Risk Factor Surveillance System. We then analyze cross-lag models to determine whether greater retailer density drives county smoking prevalence or whether retailers locate in areas with high demand for tobacco. Aim 3 integrates cancer, cardiovascular and pulmonary disease, and birth outcomes incidence data from the North American Association of Central Cancer Registries (NACCR), the Healthcare Cost and Utility Project (HCUP), and the National Vital Statistics System (NVSS) to estimate potential population level health effects of capping tobacco retailer density. Evidence regarding the effect of retail density on smoking is emerging, but questions remain about temporality and ultimate impact on health. The proposed work is the first to longitudinally examine these associations, substantially strengthening causal inference, and is also the first to examine associations between tobacco retailer density and subsequent tobacco-related health effects, including cancer.