Minimally invasive radio-guided parathyroidectomy (MIRP) has had a high success rate in correcting hypercalcemia, along with a low morbidity rate and high patient satisfaction. Our study was conducted in an attempt to analyze the cost-effectiveness of MIRP in patients treated for primary hyperparathyroidism. We conducted a retrospective study of the total charges of three groups of patients undergoing surgery for previously untreated hyperparathyroidism in a single health care system. The three study groups included patients undergoing traditional bilateral neck exploration, MIRP, and neck exploration guided by intraoperative parathormone (PTH) assay. Charges were stratified into preoperative, intraoperative, and postoperative categories. The average total charge was $8,512 for MIRP, $12,723 for traditional neck exploration, and $13,011 for bilateral neck exploration with PTH assay. The decreased charge for MIRP was due to reduced operating room time, anesthesia costs, length of hospitalization, and an avoidance of the use of intraoperative tissue analysis and PTH assay. There was a greater than $4,000 savings with MIRP as compared with the more extensive neck exploration. These savings more than compensate for the cost of technology (preoperative sestamibi scan and intraoperative gamma probe) necessary to perform radio-guided parathyroidectomy.