Minimally invasive parathyroidectomy (MIP) has become the preferred surgical treatment for selected patients diagnosed with primary hyperparathyroidism (PHPT) at our tertiary-care center. Preoperative scintigraphy establishes the position of a parathyroid adenoma, dictates the incision site, and can minimize incision size and consequent tissue dissection. We reviewed our database and sought to identify factors that led to discordant preoperative imaging and operative findings and to assess the effect of experience on these findings. A retrospective review was performed on all patients with biochemically proven PHPT who underwent Tc-99m sestamibi scintigraphy and surgical intervention. Patient demographics, date of surgical intervention, scintigraphic localization, surgical findings, pre- and postoperative biochemical markers, histopathology, coexisting thyroid pathology, and 6-month follow up were recorded. Preoperative images that were discordant with operative findings were independently reviewed. Parathyroid scintigraphy was performed on 125 consecutive patients for PHPT between November 1999 and January 2002. Seventy-six patients had MIPs, 35 had standard cervical explorations, 11 had MIPs that were converted to standard cervical explorations, and three had surgery directed to an ectopic location. At 6-month follow-up 98.4 per cent were cured. Preoperative imaging and surgical findings were ipsilateral and concordant in 105 of 118 (89%) patients with parathyroid adenoma. The anatomic origin of an adenoma was predicted in only 83 of 118 (68%) patients. Most of the inaccurate scintigraphy readings occurred during the first 13 of the 26 months that MIPs were performed at our institution. Only two discordant cases occurred during the last 9 months of this period. Biochemical markers, prior neck operation, and concomitant thyroid pathology had no correlation with imaging sensitivity. Scintigraphic interpretation of smaller adenomas was less reliable; discordant cases were more common in small adenomas. Communication between endocrine surgeons and nuclear medicine physicians about the MIP technique and anatomic orientation of adenomas led to better scintigraphic localization as experience increased. Now that MIP by skilled endocrine surgeons is becoming the favored treatment for PHPT experienced nuclear medicine physicians may be the most important factor to achieve maximum success.