To identify variables that are associated with poor compliance to thyroid hormone replacement therapy in children after total thyroidectomy. A retrospective cohort study of children who underwent total thyroidectomy by high-volume pediatric otolaryngologists between 1/2014 and 9/2021. Postoperative poor compliance was characterized by at least three separate measurements of high TSH levels not associated with radioactive iodine treatment. There were 100 patients, ages 3-20 years old who met inclusion criteria; 44 patients underwent thyroidectomy for cancer diagnosis, and 56 for Graves' disease. The mean follow-up time was 36.5 months (range 3.0-95.6 months). Overall, 42 patients (42%) were found to have at least three measurements of high TSH during follow-up, and 29 patients (29%) were diagnosed with clinical hypothyroidism. Sex, race, income, insurance type, and benign versus malignant etiology for thyroidectomy were not associated with adherence to therapy. Multivariate regression analysis identified patients with Graves' disease and hyperthyroidism at the time of surgery and Hispanic ethnicity to be associated with postoperative clinical hypothyroidism (OR 9.38, 95% CI 2.16-49.2, p=0.004 and OR 6.15, 95% CI 1.21-36.0, p=0.033, respectively). Preoperative hyperthyroidism in patients with Graves' disease and Hispanic ethnicity were predictors of postoperative TSH abnormalities. Preoperative counseling for patients and their families on the implications of total thyroidectomy and the need for life-long medications postoperatively is necessary. Efforts should be made to evaluate and improve adherence to therapy pre-and postoperatively in patients with Graves' disease. 4 Laryngoscope, 133:2402-2406, 2023.