Background: We sought to determine certain factors predicting postoperative need for hormone replacement therapy (HRT) after hemithyroidectomy. Methods: A PubMed search was conducted to identify articles with separate cohorts for total and hemithyroidectomy. Outcomes of interest included hypothyroidism and complications. Results: Of 50,445 patients, 15,412 (30.6%) underwent hemithyroidectomy. The reported incidence rate of postoperative hypothyroidism was 10.9-48.8%. The pooled mean preoperative thyroid-stimulating hormone (TSH) level was 1.06 µIU/l (0.83-1.29) higher in hypothyroid patients. A preoperative TSH level >2.5 µIU/l was associated with a relative risk (RR, 95% CI) of 3.16 (2.03-4.90) for postoperative hypothyroidism. There was a significant pooled RR of 3.52 (2.55-4.86) for thyroid antibodies and 3.30 (2.49-4.36) for thyroiditis on pathology for postoperative HRT. The pooled RR for postoperative complications was 10.67 (5.75-19.31) for temporary hypocalcemia, 3.17 (1.72-5.83) for permanent hypocalcemia, 1.69 (1.30-2.20) for temporary injury to the recurrent laryngeal nerve (RLN), 1.85 (1.28-2.69) for permanent RLN injury and 2.58 (1.69-3.93) for hemorrhage in patients who underwent total thyroidectomy compared to hemithyroidectomy. Conclusion: Higher preoperative TSH levels, presence of anti-thyroid antibodies and thyroiditis predict postoperative need for HRT. It is imperative to counsel patients with these findings regarding their higher risk of developing postoperative hypothyroidism and need for HRT after hemithyroidectomy.