Background Symptomatic (SX) hypocalcemia after thyroidectomy is a barrier to same day surgery and the cause of emergency room visits. A standard protocol of calcium and vitamin D supplementation, dependent on intact parathyroid hormone (iPTH) levels, can address this issue. How effective is it? When does it fail? Methods We performed a retrospective review of the prospective Thyroid database from January 2006 to December 2010. Six hundred twenty patients underwent completion thyroidectomy or total thyroidectomy and followed our postoperative protocol of calcium carbonate administration for iPTH levels ≥10 pg/mL and calcium carbonate and 0.25 μg calcitriol twice a day for iPTH <10 pg/mL. Calcium and iPTH values, pathology, and medication were compared to evaluate protocol efficacy. A P value <0.05 was considered statistically significant. Results Using the protocol, sixty-one (10.2%) patients were chemically hypocalcemic but never developed symptoms and 24 (3.9%) patients developed breakthrough SX hypocalcemia. The SX and asymptomatic groups were similar with regard to gender, cancer diagnosis, and preoperative calcium and iPTH. The SX group was significantly younger (39.6 ± 2.8 versus 49 ± 0.6 y, P = 0.01), with lower postoperative iPTH levels. Thirty-three percent (n = 8) of SX patients had an iPTH ≤5 pg/mL versus only 6% (n = 37) of ASX patients. Although the majority of patients with a iPTH ≤5 pg/mL were asymptomatic, 62.5% (n = 5) of SX patients with iPTH levels ≤5 pg/mL required an increase in calcitriol dose to achieve both biochemical correction and symptom relief. Conclusions Prophylactic calcium and vitamin D supplementation based on postoperative iPTH levels can minimize SX hypocalcemia after thyroidectomy. An iPTH ≤5 pg/mL may warrant higher initial doses of calcitriol to prevent symptoms. © 2014 Elsevier Inc. All rights reserved.