Background: Post-thyroidectomy hypocalcemia is a frequent and significant complication that can lead to considerable morbidity. Identifying reliable predictors of this condition is crucial for improving patient outcomes and managing postoperative care effectively. Aim: To determine the incidence and predictors of post-thyroidectomy hypocalcemia in patients treated at a tertiary care hospital in New Delhi. Methodology: A retrospective analysis was conducted on 117 patients who underwent total thyroidectomy between January 2021 and March 2023. Exclusion criteria included patients with prior or concomitant parathyroidectomy, known hyperparathyroidism, and preoperative hypocalcemia. Postoperative serum calcium and intact parathyroid hormone (iPTH) levels were recorded on the first postoperative day (POD1). Patients with biochemical or clinical signs of hypocalcemia were treated accordingly. Result: The incidence of transient hypocalcemia was 46.6%, with 34.16% of patients requiring intravenous calcium infusion. Low iPTH levels and postmenopausal status emerged as significant predictors of hypocalcemia. Patients with low iPTH levels were more likely to require intravenous calcium, and postmenopausal women showed a higher incidence of hypocalcemia compared to premenopausal women (62.5% vs 30%). Conclusion: Low postoperative iPTH levels and postmenopausal status are significant predictors of hypocalcemia in patients undergoing total thyroidectomy. These findings can help in developing targeted management strategies to mitigate the risk of hypocalcemia. Recommendation: Routine measurement of iPTH levels on postoperative day 1 (POD1) should be incorporated into postoperative care protocols to identify patients at risk for hypocalcemia. Special attention should be given to postmenopausal women, and early intervention strategies should be implemented to improve patient outcomes and reduce hospital stay duration. Further prospective studies with larger sample sizes are recommended to validate these findings.