OBJECTIVES:: To determine the budget impact of incorporating a levothyroxine gel cap formulation in the treatment of patients diagnosed with hypothyroidism that require dose changes secondary to gastrointestinal disease, suboptimal absorption, or tolerability issues with tablet formulations. METHODS::  Costs of levothyroxine formulations (tablets/gel caps; branded/generic) were obtained. Estimated utilization patterns/costs of physician services, laboratory, ancillary services, and lost productivity were based on published literature and governmental/public sources. The projected population was based on epidemiology reports and estimates from the 2014 American Association of Clinical Endocrinology/American Thyroid Association Guidelines for the Treatment of Hypothyroidism. MS Excel was used to construct the model and generate outputs. RESULTS::  For every 500,000 persons, there were 23,000 (4.6%) hypothyroid patients of which 17,480 (76.0%) received levothyroxine. The proportion of patients requiring ≥1 dosage changes annually [‘hard-to-treat’ patients] was 31.4% (n=5,489). Similarly, the proportion requiring ≥2 dosage changes annually [‘harder-to-treat’] patients was 8.0% (n=1,398). Using evidenced-based data of the tolerability/absorption of levothyroxine gel caps and converting 20.0% of ‘hard-to-treat’ patients to this formulation produced an annual net cost savings of 294,045 (US$) in direct medical costs and 1,708,684 (US$) in lost productivity. Converting 20.0% of ‘harder-to-treat patients,’ produced an annual net cost savings of 74,916 (US$) in direct medical costs and 435,334 (US$) in lost productivity. The component reduction in direct medical costs was 15.8% for emergency visits, 15.2% for hospitalizations, 6.9% for laboratory, 6.1% for office visits, and 2.7% for specialist visits. The net savings included additional drug costs of the gel cap formulation of 1,288,809 (US$) in the ‘hard-to-treat’ scenario and 328,359 (US$) in the ‘harder-to-treat’ scenario. CONCLUSIONS:: Hypothyroidism can be adequately treated with a consistent daily dose of levothyroxine. However, the need for dose adjustment does occur amongst certain patients. For patients requiring ≥1 dosage changes annually, consideration of switching from tablet to gel cap formulation is warranted.