Objective To determine whether food insecurity, limited or uncertain food access owing to cost, is associated with greater health care expenditures. Data Source/Study Setting Nationally representative sample of the civilian noninstitutionalized population of the United States (2011 National Health Interview Survey [NHIS] linked to 2012–2013 Medication Expenditure Panel Survey [MEPS]). Study Design Longitudinal retrospective cohort. Data Collection/Extraction Methods A total of 16,663 individuals underwent assessment of food insecurity, using the 10‐item adult 30‐day food security module, in the 2011 NHIS. Their total health care expenditures in 2012 and 2013 were recorded in MEPS. Expenditure data were analyzed using zero‐inflated negative binomial regression and adjusted for age, gender, race/ethnicity, education, income, insurance, and residence area. Principal Findings Fourteen percent of individuals reported food insecurity, representing 41,616,255 Americans. Mean annualized total expenditures were $4,113 (standard error $115); 9.2 percent of all individuals had no health care expenditures. In multivariable analyses, those with food insecurity had significantly greater estimated mean annualized health care expenditures ($6,072 vs. $4,208, p < .0001), an extra $1,863 in health care expenditure per year, or $77.5 billion in additional health care expenditure annually. Conclusions Food insecurity was associated with greater subsequent health care expenditures. Future studies should determine whether food insecurity interventions can improve health and reduce health care costs.