BACKGROUND The favorable prognostic significance of normal 201Tl stress perfusion images, even in the presence of known coronary artery disease, has been well documented. Relatively few data are available with regard to the prognostic significance of normal planar and single-photon emission computed tomographic (SPECT) stress 99mTc-labeled sestamibi (99mTc-sestamibi) images. RESULTS The prognostic significance of normal exercise 99mTc-sestamibi myocardial perfusion imaging was evaluated in 208 consecutive patients. All patients were referred for evaluation of chest pain syndrome. One hundred eight patients (52%) underwent SPECT imaging, 79 patients (38%) underwent planar imaging, and 21 patients (10%) underwent both planar and SPECT imaging. One hundred seventy-five patients (84%) had a normal or nondiagnostic exercise electrocardiogram, and 33 patients (16%) had a positive exercise electrocardiogram. Follow-up was 13.5 +/- 2 months and was complete in 99.5% of patients. No patient died of cardiac causes during follow-up. One patient (0.5%) had a nonfatal myocardial infarction and four patients (2%) had unstable angina necessitating revascularization. There was no difference in rate of cardiac events between men and women or whether SPECT or planar imaging was used. However, 33 patients with normal 99mTc-sestamibi imaging and a positive exercise electrocardiogram had a significantly higher cardiac event rate than had patients with negative exercise electrocardiograms (9% vs 1%, p < 0.025). CONCLUSIONS Patients with normal 99mTc-sestamibi exercise SPECT or planar imaging results and a normal or nondiagnostic exercise electrocardiogram have a favorable 1-year prognosis. Patients with normal 99mTc-sestamibi images and a positive stress electrocardiogram have a less favorable outcome.