The Prevention Impacts Simulation Model (PRISM) projects the multiyear impacts of 22 different interventions aimed at reducing risk of cardiovascular disease. We grouped these into 4 categories: clinical, behavioral support, health promotion and access, and taxes and regulation. We simulated impacts for the United States overall and also for a less-advantaged county with a higher death rate. Of the 4 categories of intervention, taxes and regulation reduce costs the most in the short term (through 2020) and long term (through 2040) and reduce deaths the most in the long term; they are second to clinical interventions in reducing deaths in the short term. All 4 categories combined were required to bring costs and deaths in the less-advantaged county down to the national level.