Numerous local interventions for cardiovascular disease are available, but resources to deliver them are limited. Identifying the most effective interventions is challenging because cardiovascular risks develop through causal pathways and gradual accumulations that defy simple calculation. We created a simulation model for evaluating multiple approaches to preventing and managing cardiovascular risks. The model incorporates data from many sources to represent all US adults who have never had a cardiovascular event. It simulates trajectories for the leading direct and indirect risk factors from 1990 to 2040 and evaluates 19 interventions. The main outcomes are first-time cardiovascular events and consequent deaths, as well as total consequence costs, which combine medical expenditures and productivity costs associated with cardiovascular events and risk factors. We used sensitivity analyses to examine the significance of uncertain parameters. A base case scenario shows that population turnover and aging strongly influence the future trajectories of several risk factors. At least 15 of 19 interventions are potentially cost saving and could reduce deaths from first cardiovascular events by approximately 20% and total consequence costs by 26%. Some interventions act quickly to reduce deaths, while others more gradually reduce costs related to risk factors. Although the model is still evolving, the simulated experiments reported here can inform policy and spending decisions.