OBJECTIVES: Thyroid cancer (TC) constitutes ~1% of all diagnosed cancers. DTC is the most common type of TC, accounting for about 95% of all cases. Most patients with DTC respond well to surgery and/or radioiodine therapy (I-131). However, <5% of patients become refractory to I-131. Disease burden and healthcare costs associated with this orphan disease have not been well described.  METHODS: This retrospective cohort analysis combined data from the Humana and OptumInsight Claims databases from Apr2005-Jun2014. Patients age >=18 years were defined as having RAI-R DTC if they received a tyrosine-kinase inhibitor (TKI) and had >=2 diagnoses of thyroid cancer (ICD-9 code 193.xx) on or prior to the index date (first TKI use). Patients were excluded if no continuous medical/pharmacy coverage in the 6-months pre and post-index. Descriptive results included mean all-cause and thyroid-related total healthcare cost & utilization (inpatient, outpatient and pharmacy), and were assessed 6 months post-index then converted to annual estimates. Results were reported for both the individual and combined datasets.  RESULTS: A total of 116 patients ( Humana=36; Optum=80 patients) were identified. Mean age was 60 years and 45.7% were female. The average time from diagnosis to TKI use was 754 days. The most common TKIs were sorafenib (41.4%), sunitinib (26.7%), and vandetanib (14.7%), and 31.9% of patients used >=2 TKIs. The average number of outpatient and ER visits were 43.4 and 1.2 for all-cause, and 22.2 and 0.3 for thyroid-related, respectively.  Rates of hospitalization were 25.0% and 11.2% for all- and thyroid-related causes, with a mean stay of 7.8 and 5.1days, respectively. The average number of all-cause and thyroid-related prescriptions were 40.9 and 15.7, respectively. Total all- and thyroid-related annual healthcare costs were $127,935 and $97,344, respectively.  CONCLUSIONS: RAI-R DTC is a rare disease, with high disease burden as shown through high rates of healthcare utilization and annual cost.