Background Poor diet is a leading risk factor for cardiometabolic disease (CMD) in the United States, but its economic costs are unknown. We sought to estimate the cost associated with suboptimal diet in the US. Methods and findings A validated microsimulation model (Cardiovascular Disease Policy Model for Risk, Events, Detection, Interventions, Costs, and Trends [CVD PREDICT]) was used to estimate annual cardiovascular disease (fatal and nonfatal myocardial infarction, angina, and stroke) and type 2 diabetes costs associated with suboptimal intake of 10 food groups (fruits, vegetables, nuts/seeds, whole grains, unprocessed red meats, processed meats, sugar-sweetened beverages, polyunsaturated fats, seafood omega-3 fats, sodium). A representative US population sample of individuals aged 35-85 years was created using weighted sampling from National Health And Nutrition Examination Surveys (NHANES) 2009-2012 cycles. Estimates were stratified by cost type (acute, chronic, drug), sex, age, race, education, BMI, and health insurance. Annual diet-related CMD costs were $301/person (95% CI $287-$316). This translates to $50.4 billion in CMD costs (18.2% of total) for the whole population, of which 84.3% are attributed to acute care ($42.6 billion). The largest annual per capita costs are attributed to low consumption of nuts/seeds ($81; 95% CI $74-$86) and seafood omega-3 fats ($76; 95% CI $70-$83), and the lowest are attributed to high consumption of red meat ($3; 95% CI $2.8-$3.5) and polyunsaturated fats ($20; 95% CI $19-$22). Individual costs are highest for men ($380), those aged >= 65 years ($408), blacks ($320), the less educated ($392), and those with Medicare ($481) or dual-eligible ($536) insurance coverage. A limitation of our study is that dietary intake data were assessed from 24-hour dietary recall, which may not fully capture a diet over a person's life span and is subject to measurement errors. Conclusions Suboptimal diet of 10 dietary factors accounts for 18.2% of all ischemic heart disease, stroke, and type 2 diabetes costs in the US, highlighting that timely implementation of diet policies could address these health and economic burdens. Author summaryWhy was this study done? Unhealthy diet is responsible for up to 45% of all cardiometabolic disease (CMD) deaths. In addition to the health impact, CMDs pose a substantial economic burden. Despite the clear association between poor diet and CMD, the costs of a suboptimal diet pattern in the US have not been estimated. We sought to estimate the CMD-related cost associated with suboptimal diet in the US. What did the researchers do and find? We used a microsimulation model to estimate annual cardiovascular disease (CVD) and type 2 diabetes costs associated with suboptimal intake of 10 food groups. A representative US population sample of individuals aged 35-85 years was created from National Health And Nutrition Examination Surveys (NHANES) 2009-2012 cycles. Annual diet-related CMD costs were $301/person, which translates to $50.4 billion for the whole population (18.2% of total costs). The largest annual per capita costs are attributed to low consumption of nuts/seeds ($81) and seafood omega-3 fats ($76), and the lowest are attributed to high consumption of red meat ($3) and polyunsaturated fats ($20). Individual costs are highest for men ($380), those aged >= 65 years ($408), blacks ($320), the less educated ($392), and those with Medicare ($481) or dual-eligible ($536) insurance coverage. What do these findings mean? The CMD costs estimated to be associated with suboptimal diet highlight the need to implement diet policies to address health and economic burdens. The high CMD-related costs associated with suboptimal diet combined with the finding that the cost burden often falls upon the government illustrates the need for community and policy strategies to reduce this financial burden.