Abstract Purpose Overuse of thyroid ultrasound (TUS) has contributed to rising thyroid cancer diagnoses and is projected to increase US healthcare costs from $1.5 billion to $3.5 billion by 2030. This study evaluated the healthcare cost of inappropriately ordered TUS in a national multicenter academic system. Methods This is a secondary cost analysis of a retrospective cohort study across 4 Mayo Clinic sites (Rochester, MN; Jacksonville, FL; Scottsdale, AZ; and the Midwest Mayo Clinic Health System). Adult patients (≥18 years) undergoing their first TUS between January 1, 2017, and December 31, 2021, with at least 1 year of follow-up were included. TUS indications were classified as appropriate or inappropriate using a guideline-based natural language processing algorithm. The primary outcome was a comparison of adjusted 1-year all-cause healthcare costs. A secondary analysis calculated the direct procedural costs of the inappropriate TUS cascade. Results Among 6984 patients (mean age 56 [SD 16.4]; 76.2% female; 90.9% White), 546 (7.8%) underwent TUS for inappropriate indications. These patients were younger (mean age 53.0 vs 56.3 years, P < .0001) but otherwise demographically similar. Adjusted total healthcare costs over 90 days and 1 year were comparable: $4842 vs $5794 and $13 748 vs $14 257 for inappropriate vs appropriate TUS, respectively. The inappropriate TUS cascade, including an estimated 56 subsequent biopsies and 22 thyroidectomies, resulted in a minimum of $576 134 in direct procedural costs. Conclusion While adjusted total costs were similar, inappropriate TUS represents potentially avoidable spending and remains a viable target for cost-reduction strategies. Reducing low-value imaging remains a critical target for cost-saving interventions.