OBJECTIVES: To estimate the direct medical costs and indirect costs of food-induced allergic reactions and anaphylaxis in the U.S.  METHODS: Costs were estimated with a bottom-up approach from a societal perspective: the average cost of illness per patient was calculated and multiplied by reported prevalence estimates. Patients with an inpatient admission, emergency department admission, office-based physician visit, or outpatient visit for a food-induced allergic reaction were identified from a list of federally administered 2006 and 2007 databases by using ICD-9 codes. Indirect costs were quantified by estimating the lost productivity, in terms of lost earnings due to absenteeism and mortality, of patients or caregivers. Sensitivity analyses were conducted to measure the robustness of the estimates. RESULTS: For 2007, direct medical costs were $225 million and indirect costs were $115 million. Office visits accounted for 52.5% of costs, and the remainder was split between emergency visits (20%), inpatient hospitalizations (11.8%), outpatient visits (3.9%), ambulance runs (3%), and epinephrine devices (8.7%). Simulations from probabilistic sensitivity analyses suggested mean direct medical costs were $307 million and indirect costs were $203 million. CONCLUSIONS: The economic burden of allergic reactions due to food and anaphylaxis was an estimated half a billion dollars in 2007. Ambulatory visits accounted for more than one half of costs.