A 24- to 48-hour in-hospital observation period to monitor for hypocalcemia is common after total thyroidectomy. Because most thyroidectomy patients do not experience this potentially serious complication, investigators have searched for methods and clinical indicators that may help stratify thyroidectomy patients according to their risk of developing hypocalcemia and identify those who can be safely discharged earlier. We conducted a retrospective study to compare the value of an immediate postoperative intact parathyroid hormone (PTH) level and serial calcium levels in predicting the development of hypocalcemia following total thyroidectomy. Our study population was made up of 69 consecutive patients who had undergone total thyroidectomy from January 2004 through March 2005. These patients were divided into two groups on the basis of their postoperative calcium levels; 11 patients (16%) had developed transient hypocalcemia (serum calcium level: <7.5 mg/dl) and 58 (84%) had remained normocalcemic. A model was developed to assess the relationship between early (<60 min) postoperative PTH levels and serial (6 and 18 hr) calcium levels, and the two-sample Student t test was used to identify differences between the two groups. Analysis showed that hypocalcemia was associated with a postoperative PTH level of less than 14 pg/ml and a negative serum calcium slope between 6 and 18 hours postoperatively. A single early postoperative intact PTH measurement may be the most cost-effective screening tool for hypocalcemia, but even greater specificity can be achieved by combining those findings with a serum calcium measurement taken 6 hours postoperatively. The combination of the two measurements represents the safest method of assessing risk and identifying those patients who can be discharged on the day of surgery.