While short-term studies of the adverse effects of air pollution have found regional differences, there has been insufficient evidence from long-term studies. This study investigated the spatial variation of the association between long-term exposure to particulate matter (PM) air pollution and cardiovascular disease (CVD) incidence and their relevant regional characteristics. We selected 155,017 adults who have lived over 13 years in each of the 16 regions of South Korea from the National Health Insurance Service-National Sample Cohort. We assessed the individual long-term exposure as a 5-year average concentration at district-level residential addresses estimated by previously validated exposure prediction models. We applied time-dependent Cox-proportional hazard models to explore the spatial variation of long-term PM exposure's association with CVD incidence. After adjusting for individual-level characteristics, we estimated the region-specific hazard ratios (HRs) of incident CVD per 10 μg/m