A combination of preoperative localization and intraoperative parathormone (PTH) monitoring permits targeted parathyroidectomy. Multiple approaches have been developed, ranging from unilateral neck exploration (UE) to radio-guided parathyroidectomy (RP) to endoscopic parathyroidectomy (EP). The purpose of this study was to evaluate the efficacy of these approaches in the management of primary hyperparathyroidism. From June 1998 to November 2000 a total of 110 targeted parathyroid operations were performed at a university medical center. All patients underwent technetium-99m-sestamibi scanning, ultrasonography, or both prior to surgery. Intraoperative PTH monitoring was utilized in all cases. Thirty-seven patients underwent UE, 59 underwent RP, and 14 underwent EP. Follow-up ranged from 1 to 24 months. All patients were cured following parathyroidectomy as predicted by a more than 50% reduction of the intraoperative PTH level following removal of all hypersecreting glands. Altogether, 103 patients had a solitary adenoma (95%), and 1 patient had a parathyroid carcinoma. Six patients (5%) had multigland disease, including four cases of hyperplasia and two patients with a double adenoma. Eighty-three patients (75%) were discharged the day of surgery. The use of preoperative localization and intraoperative PTH monitoring permits a targeted approach to the treatment of primary hyperparathyroidism. Endocrine surgeons should be facile in all minimally invasive parathyroid techniques to individualize the operative approach.