Background: The risk and effect of hypocalcemia following surgery of different magnitudes remains unclear. Thus, we assessed whether different extents of central lymph node dissection (CLND) and status of preserved parathyroid glands can influence parathyroid function in differentiated thyroid carcinoma (DTC) patients with initial surgical resection. Methods: Participants were categorized into 6 groups based on the extent of the surgical procedures, number of parathyroid glands preserved in situ, and parathyroid autotransplantation. The frequencies of hypocalcemia, serum calcium (Ca) levels, and parathyroid hormone (PTH) levels among the different groups were analyzed. Results: The prevalence of hypocalcemia, number and status of parathyroid glands preserved in situ, and parathyroid autotransplantation were inversely related to extensive CLND (r=−0.18; P<0.05). The decrease of serum Ca and PTH was most severe on postoperative days (POD) 1–7. The incidence of hypocalcemia was higher in Group C than in Group B and A (P<0.05). The average postoperative serum Ca and PTH levels in Group C were significantly lower than group A on POD 1–7 (P<0.05). The incidence of hypocalcemia was obviously increased in Group D compared to Groups E and F (P<0.05). The mean serum Ca and PTH levels in Group D were significantly lower than in Group F (P<0.05), and the same results could be observed between Groups D and E (P<0.05). However, through parathyroid autotransplantation, there was no significant difference that could be found between Groups E and F on POD 1–7 (P>0.05). Conclusions: With the expansion of CLND scope, postoperative parathyroid function will be affected, increasing the risk of postoperative hypocalcemia. When at least 1–2 parathyroid glands were reserved in situ plus at least 1 parathyroid gland autotransplantation, there was little effect on postoperative parathyroid function. © Gland Surgery. All rights reserved.