Background Despite thyroid hormone replacement, some euthyroid patients with Hashimoto thyroiditis will continue to experience persistent symptoms that reduce their quality of life. Recent studies indicate that total thyroidectomy is superior to medical therapy alone in improving these symptoms. However, there is a high complication rate after total thyroidectomy in patients with Hashimoto thyroiditis. This study evaluates the cost-effectiveness of total thyroidectomy for euthyroid patients who have Hashimoto thyroiditis with persistent symptoms. Methods We utilized a Markov model to compare total thyroidectomy and medical therapy alone over the lifetime of the cohort. Costs, probabilities, and utility parameters were derived from literature and Medicare cost data. A willingness-to-pay threshold of $100,000/quality-adjusted life years was used. We performed sensitivity analyses to ascertain model uncertainty. Results On average, medical therapy alone costs $12,845, produced 16.9 quality-adjusted life years, and was dominated. Total thyroidectomy costs $1,490 less and produced 1.4 more quality-adjusted life years. Probabilistic sensitivity analysis confirmed total thyroidectomy as the optimal strategy in 89% of cases. Medical therapy alone will become cost-effective if the cost of uncomplicated thyroidectomy increases by 25%, if the probability of permanent complication after total thyroidectomy increases 12-fold, or if there is no gain in quality of life after thyroidectomy. Conclusion Total thyroidectomy is more cost-effective than medical therapy alone for the management of euthyroid patients who have Hashimoto thyroiditis with persistent symptoms.