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Objective: To improve food insecurity interventions, we sought to better understand the hypothesized bidirectional relationship between food insecurity and health care expenditures.Data Source: Nationally representative sample of the civilian noninstitutionalized population of the United States (2016-2017 Medical Expenditure Panel Survey [MEPS]).Study Design: In a retrospective longitudinal cohort, we conducted two sets of analyses: (a) two-part models to examine the association between food insecurity in 2016 and health care expenditures in 2017; and (b) logistic regression models to examine the association between health care expenditures in 2016 and food insecurity in 2017. We adjusted for demographic and socioeconomic variables as well as 2016 health care expenditures and food insecurity.Data Collection: Health care expenditures, food insecurity, and medical condition data from 10 886 adults who were included in 2016-2017 MEPS.Principal Findings: Food insecurity in 2016, compared with being food secure, was associated with both a higher odds of having any health care expenditures in 2017 (OR 1.29, 95% CI: 1.04 to 1.60) and greater total expenditures ($1738.88 greater, 95% CI: $354.10 to $3123.57), which represents approximately 25% greater expenditures. Greater 2016 health care expenditures were associated with slightly higher odds of being food insecure in 2017 (OR 1.007 per $1000 in expenditures, 95% CI: 1.002 to 1.012, P =0.01). Exploratory analyses suggested that poor health status may underlie the relationship between food insecurity and health care expenditures.Conclusions: A bidirectional relationship exists between food insecurity and health care expenditures, but the strength of either direction appears unequal. Higher health care expenditures are associated with a slightly greater risk of being food insecure (adjusted for baseline food insecurity status) but being food insecure is associated with substantially greater subsequent health care expenditures (adjusted for baseline health care expenditures). Interventions to address food insecurity and poor health may be helpful to break this cycle. [ABSTRACT FROM AUTHOR]