Background: The standard surgical procedure for parathyroidectomy consists of bilateral cervical exploration and the visualization of all four parathyroid glands. However, improved preoperative localization techniques and the availability of intraoperative intact parathyroid hormone (iPTH) monitoring now allow single adenomas to be treated with minimally invasive techniques. Methods: Patients with primary hyperthyroidism (pHPT), who were found to have one unequivocally enlarged parathyroid gland on preoperative ultrasound and Tc-99m-SestaMIBI scintigraphy underwent minimally invasive video-assisted parathyroidectomy by an anterior approach. Intraoperatively rapid electrochemiluminescense immunoassay was used to measure iPTH levels shortly before and 5, 10, and 15 mins after excision of the adenoma. The operation was considered successful when a > 50% decrease in preexcision iPTH levels was observed after 5 min, Results: Between November 1999 and May 2000, 10 of 22 patients with pHPT were deemed eligible for the minimally invasive approach. In all cases, the adenoma was removed successfully. However, in two cases, intraoperative. iPTH monitoring did not show a sufficient decrease in iPTH values. Subsequent cervical exploration revealed a double adenoma in one case and hyperplasia in the other. Conclusions: Even when high-resolution ultrasound and Tc-99m-SestaMIBI scintigraphy are used, the presence of multiple glandular desease cannot be ruled out entirely. When the minimally invasive approach is contemplated, intraoperative iPTH monitoring is indispensible to ensure operative success. However, in selected cases, minimally invasive parathyroidectomy represents an excellent alternative to the conventional technique.