OBJECTIVES: To examine the direct (resource utilization and associated medical cost) and indirect (productivity costs) economic burden associated with hypothyroidism in the United States. METHODS: Using the Truven Health MarketScan^® databases, patients who received 2 or more diagnoses of hypothyroidism in the calendar years 2012, 2013 or 2014 were identified (N=834,713) and examined for 1 year post initial diagnosis of hypothyroidism (index date). Healthy controls were matched 1:1 to the hypothyroidism cohort based upon patient characteristics (age, sex, region, and insurance type) and availability of productivity data (absenteeism, short-term disability [STD], long-term disability [LTD], and worker’s compensation [WC]). Multivariable analyses compared resource utilization, annual medical costs, and productivity costs between hypothyroidism and controls. RESULTS: Hypothyroidism was associated with a significantly higher probability of hospitalization (8.79% v 5.05%; OR 1.53, 95% CI 1.52-1.55) or ER visit (21.71% v 14.99%; OR 1.74, 95% CI 1.72-1.76) and a longer hospital length of stay (1.00 v 0.42 days) compared to controls (all P<0.0001). This additional utilization is consistent with the finding of incremental annual total medical costs of $6,928 per patient associated with hypothyroidism. Specifically, patients with hypothyroidism (N=799,466), compared to healthy controls (N=799,466) had significantly higher total medical costs ($15,737 v $8,809), as well as significantly higher inpatient ($3,027 v $1,495), outpatient ($6,456 v $3,973), emergency room (ER) ($733 v $423), drug ($5,637 v $3,273), and laboratory costs ($104 v $50) (all P<0.0001). For the subset of patients with available productivity data, patients with hypothyroidism, compared to controls, had significantly higher costs associated with absenteeism ($5,946 v $5,775), STD ($414 v $300), LTD ($36 v $19) (all P<0.0001) but significantly lower WC costs ($49 v $55; P<0.0001). CONCLUSIONS: Findings of this large study demonstrate the substantial direct and indirect economic burden associated with hypothyroidism.