Background. Despite the high cure rate and low morbidity of bilateral neck exploration for primary hyperparathyroidism, there is a movement toward minimizing the process in terms of incision, cost, extent of exploration, and length of hospital stay, while maintaining excellent outcomes. Methods: Between March and November 1998, 33 patients with primary hyperparathyroidism underwent minimally invasive parathyroidectomy. All had preoperative sestamibi-SPECT scans suggesting a single adenoma, underwent anterior cervical block anesthesia by the surgeon, and were explored through a 1- to 4-cm incision. Intraoperative parathyroid hormone assays were performed before and 5 to 10 minutes after parathyroid resection. Outcomes were compared with those of 184 consecutive patients who underwent bilateral parathyroid exploration under general anesthesia by the same surgeon between August 1990 and May 1996. Results. The mean age of the patients undergoing minimally invasive parathyroidectomy was 61 ± 2 years, and 24 of the 33 patients were women. Thirty (91%) had resection of a single adenoma under regional anesthesia; 26 of these were done as outpatient procedures. Three patients underwent conversion to general anesthesia for bilateral exploration and were found to have multigland disease (two double adenomas, one hyperplasia). All 33 patients were normocalcemic postoperatively. There was no morbidity. When the minimally invasive parathyroidectomy and bilateral parathyroid exploration groups were compared, they were found to be similar with respect of age, preoperative calcium and parathyroid hormone levels, cause of primary hyperparathyroidism, weight of resected glands, cure rates, and morbidity. However, the minimally invasive parathyroidectomy group had a significantly shorter length of hospital stay (0.3 ± 0.2 vs 1.8 ± 0.1 days, P < .001) and lower costs ($3174 ± $386 vs $6328 ± 292, P < .001). Conclusions. Minimally invasive parathyroidectomy is a safe, cost-effective alternative to bilateral exploration and may be the procedure of choice for select patients with primary hyperparathyroidism.