Recent studies have reported high sensitivities for parathyroid localization with 99mTc-sestamibi and have been performed using either 123I/99mTc-sestamibi or a double-phase sestamibi scanning technique. These studies have focused primarily on patients undergoing initial surgery. We studied 35 patients prior to reoperative surgery to investigate the relative sensitivities of these two technique sin this patient population. METHODS Double-phase sestamibi scanning (early and delayed imaging) was performed in all patients. Evaluable 123I/99mTc-sestamibi subtraction studies were also obtained in 25 patients. Results were correlated with surgical findings in 32 patients and with clinical outcome in 3 patients in whom mediastinal lesions were radiographically ablated. RESULTS Overall, double-phase sestamibi imaging detected 23 of 39 abnormal parathyroid glands (59%), whereas 123I/99mTc-sestamibi detected 19 of 27 (70%). Oblique imaging, delayed imaging and 123I subtraction all contributed to sensitivity, and 123I subtraction also proved useful in patients with partial thyroid suppression. Two patients had lesions visible on the early sestamibi images that were not seen at all on the delayed scans. There were four false-positive findings. CONCLUSIONS No significant differences between double-phase sestamibi and 123I/99mTc-sestamibi subtraction scanning were found, although the latter tended to be more sensitive.