Background: Near-infrared autofluorescence (NIRAF) imaging is known to reduce the incidence of post-thyroidectomy hypocalcemia. However, there are no studies on how much NIRAF imaging affects the serum parathyroid hormone (PTH) level after surgery. We investigated the changes of the serum PTH level and ionized calcium (iCa.) in patients undergoing total thyroidectomy with central neck dissection (CND). Materials and Methods: This retrospective study with historical control enrolled 542 patients who underwent total thyroidectomy with CND. Patients were divided into two groups: the NIRAF group (261 patients) and the control group (281 patients). PTH and iCa. levels were measured at the hospital stay, 1, 3, and 6 months after surgery. In addition, the number of identified parathyroid glands (PGs), autotransplanted PGs, and the inadvertent resection rate of PGs was evaluated. Results: The incidence of postoperative hypoparathyroidism (PTH <15 pg/mL) was significantly lower in the NIRAF group during the hospitalization (88 patients: 33.7% vs. 131 patients: 46.6%; p = 0.002) and at 1 month postoperatively (23 patients: 8.8% vs. 53 patients: 18.9%; p = 0.001). There was no difference in the permanent hypoparathyroidism rate (6 months after surgery) between the NIRAF group and the control group (4.2% vs. 4.6%; p = 0.816). There was no difference in the incidence of hypocalcemia (iCa. <1.09 mmol/L) (during hospitalization: 6.5% vs. 10.0%; 1 month: 2.3% vs. 2.5%; 3 months: 0.8% vs. 0.7%; 6 months after surgery: 1.1% vs. 1.1%) between the two groups. The number of inadvertently resected PGs was significantly lower in the NIRAF group (18:6.9% vs. 36:12.8%; p = 0.021). Conclusions: These results suggest that NIRAF imaging may reduce temporary hypoparathyroidism and the risk of inadvertent resection of PGs in patients undergoing total thyroidectomy with CND.

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