A prospective study was performed to evaluate the efficacy of technetium-99m-sestamibi and technetium-99m-pertechnetate subtraction scanning and US for imaging parathyroid glands in primary hyperparathyroidism. Sixty-three patients were surgically treated for primary hyperparathyroidism (HPT). Preoperative scintigraphy and US were performed in all cases. Bilateral neck exploration was carried out on each patient. Results of radionuclide studies and US were compared with surgical and histological findings. In 57 patients with primary HPT the radionuclide scanning gave true-positive results. Four false-negative and two false-positive scintigrams were obtained. The sensitivity and the positive predictive value (PPV) of scintigraphy were 93 and 97%, respectively. Forty-one cases were correctly localized by the US. Seventeen US results were false negative and five were false positive. The sensitivity and the PPV for US were 71 and 89%, respectively. There was a statistically significant difference between the sensitivity of the scintigraphy compared with the US ( p=0.001). Sensitivities of radionuclide scans and US were higher for adenomas (100 and 83%) than for hyperplastic glands (75 and 40%). The sensitivity of technetium-99m-sestamibi and technetium-99m-pertechnetate subtraction scintigraphy was significantly higher compared with US. This sensitive method could help surgeons in performing a rapid and directed parathyroidectomy.