Preoperative localization is essential for successful directed, minimally invasive or reoperative parathyroidectomy. Standard technetium Tc 99m-sestamibi imaging is the most sensitive modality for localization. We reviewed our experience with (99m)Tc-sestamibi imaging and specifically investigated the effect of thyroid suppression on repeat imaging of patients who had initially nonlocalizing scans.. The records of patients who underwent (99m)Tc-sestamibi imaging during evaluation for primary hyperparathyroidism were reviewed. A subset of patients with initially nonlocalizing scans underwent thyroid suppression with either thyroxin or liothyronine and then had their scans repeated.Ninety-nine patients with primary hyperparathyroidism underwent (99m)Tc-sestamibi imaging followed by parathyroidectomy (initial operation, 78; reoperation, 21). Successful parathyroid localization was obtained on standard imaging in 67 patients. Fourteen of 32 patients who had nonlocalizing (99m)Tc-sestamibi imaging studies underwent an additional scan after thyroid suppression. In 10 of 14 patients (71%), repeat (99m)Tc-sestamibi imaging after thyroid suppression successfully localized abnormal parathyroid tissue.Thyroid suppression may improve the yield of (99m)Tc-sestamibi imaging in patients with hyperparathyroidism who have an initially nonlocalizing study. This diagnostic strategy may be helpful in patients motivated to undergo a directed, minimally invasive operation, as well as in the evaluation of patients for reoperative parathyroidectomy.