Background: Improvements in the accuracy of pre-operative localization and the availability of the rapid parathyroid hormone assay have permitted minimally invasive parathyroidectomy in patients with primary hyperparathyoidism. Hypothesis: The use of intraoperative radioguidance is beneficial during targeted parathyroid operations. Design: A retrospective analysis of a prospective database of patients. Setting: Tertiary care referral center. Patients: During a 2 1/2-year period, 130 patients underwent minimally invasive, targeted parathyroidectomy with intraoperative monitoring of the parathyroid hormone level. Of these, 60 patients underwent radioguided parathyroidectomy. Prior to surgery, a solitary parathyroid adenoma was visualized on technetium Tc 99m sestamibi scintigraphy in all patients selected for radioguided parathyroidectomy. A gamma probe was used to guide the surgical dissection. Results: All patients were cured following radioguided parathyroidectomy. In 29 patients (48%), the probe provided confusing or inaccurate information; however, a unilateral neck exploration with excision of a parathyroid adenoma was successfully completed in each of these patients. Forty-three cases were completed under local anesthesia and 85% were discharged home on the same day of surgery. There was 1 temporary recurrent laryngeal nerve palsy. Conclusion: In the era of improved preoperative localization and intraoperative parathyroid hormone monitoring, the routine use of radioguidance is not recommended during parathyroidectomy.