AIM: Routine central neck dissection for differentiated thyroid cancer (DTC) to prevent a future recurrence is still a matter of discussion, due to the increased risk of injury to parathyroid glands, without a clear demonstrable benefits in terms of long-term survival. Aim of this study was to investigate if, treating patients with total thyroidectomy (TT) without prophylactic central lymphadenectomy can minimize the risk of hypocalcemia by routine administration of oral calcium and vitamin D supplements, providing at the same time a low recurrence rate. METHODS: In the set of a retrospective study, 221 patients affected by DTC were enrolled. All of them underwent to TT without prophylactic central lymphadenectomy. In the early postoperative period, oral calcium 2g/d taken twice (1 g every 12 hours) and vitamin D 1 g/d taken twice (0.5 g every 12 hours) were administered; changes in serum calcium and hypocalcemia-related symptoms were recorded. Follow-up was based on neck ultrasound and monitoring of serum Tg and Tg-antibodies levels every 6 months during suppressive l-tiroxine treatment. RESULTS: Symptomatic hypocalcemia developed only in 6.3% of patients, whereas laboratory hypocalcemia developed in 10%. Hypocalcemic symptoms were minimal in 4 patients. Intravenous calcium was administered to 6 patients with severe hypocalcemic symptoms. Permanent hypocalcemia developed in two patients. CONCLUSION: Until a conclusive evidence of the actual benefit of prophylactic central lymphadenectomy in the treatment of DTC, it may be avoided. The oral calcium and vitamin D supplements can take a role in the prevention of postoperative hypocalcemia and for increasing the likelihood of a safe and early discharge from the hospital.