We performed this study to evaluate two patient groups with primary hyperparathyroidism depending on whether their abnormal gland(s) could be preoperatively imaged with sestamibi. Patients with primary hyperparathyroidism evaluated by preoperative sestamibi examination from January 1999 to June 2000 were divided into two groups depending on the ability of sestamibi to localize their disease. Records were reviewed to determine pre- and postoperative biochemical data, weight of the excised glands, and total operating room time. When the sestamibi imaging was positive a minimally invasive parathyroidectomy was performed; however, when sestamibi scanning was negative patients underwent a formal bilateral neck exploration. All 40 patients in the sestamibi-positive group and 17 of 18 patients in the sestamibi-negative group were cured of their primary hyperparathyroidism as a result of surgery. Sestamibi scanning with a minimally invasive parathyroidectomy shortens operating room time and is most effective when adenomas are large. The results of this study suggest that strategies to preoperatively increase the activity of adenomas may improve the sensitivity of sestamibi scan localization of parathyroid adenomas.