Background. The goal of the present study was to determine the actual incidence, predictive risk factors, and clinical characteristics of levothyroxine supplementation (LT4S) used for the management of hypothyroidism after hemithyroidectomy. Methods. From 2008 to 2015, we included 535 patients who underwent hemithyroidectomy. LT4S was initiated based on three major criteria: the development of overt hypothyroidism, subclinical hypothyroidism with thyroid-stimulating hormone (TSH) levels > 10 mIU/L, or subclinical hypothyroidism with TSH levels of 4.5-10 mIU/L with associated signs/symptoms. Results. During the 69-month follow-up period, 321 patients (60%) developed overall hypothyroidism following hemithyroidectomy, and 141 ultimately required LT4S, with an overall LT4S incidence of 26.4%. The most common cause of LT4S initiation was subclinical hypothyroidism with TSH levels > 10 mIU/L. In 141 patients with LT4S, the mean maintenance dose of levothyroxine was 1.34 lg/kg, and only 6 patients (4.3%) discontinued LT4S during the follow-up. The 1-, 3-, 5-, and 7-year LT4S-free survival rates of 535 patients were 88.6%, 80.2%, 73.8%, and 69.1%, respectively. Preoperative TSH levels > 2.12 mIU/L and coexistence of Hashimoto's thyroiditis were significantly associated with LT4S following hemithyroidectomy. The risk of LT4S increased by 1.401 times, as preoperative TSH levels increased by 1 mIU/L. Discussion. A quarter of patients required LT4S after hemithyroidectomy for the management of hypothyroidism, with a mean maintenance levothyroxine dose of 1.34 lg/kg. The preoperative TSH level and coexistence of Hashimoto's thyroiditis were significant predictive factors of LT4S following hemithyroidectomy.