Coronary artery disease (CAD) is the main cause of death in elderly patients. Single-photon emission computed tomography (SPECT) with technetium-99m ((99m)Tc)-labeled agents is extremely useful for the diagnosis and risk stratification of CAD in the general population. However, its prognostic value for the elderly has not been established. This study examined disease outcome in 328 patients aged 74 or older, with suspected CAD who were submitted to either pharmacological (dipyridamole) or exercise stress SPECT with (99m)Tc-sestamibi, seven of whom were completely lost to follow-up. Endpoints were defined as hard (myocardial infarction or cardiac death) or total events (myocardial infarction, cardiac death or myocardial revascularization). Mean follow-up was 34+/-15 months. During this period 24 cardiac deaths, 11 myocardial infarctions and 21 cases of revascularization were observed. Perfusion defects were found in 27.1% of patients (12.8% reversible, 6.2% partially reversible and 8.1% fixed). Abnormal studies were predominant in men, patients with chest pain and those with ST-T abnormalities in the baseline electrocardiogram (ECG) or in the exercise treadmill test. An abnormal scan was significantly associated with cardiac events (P<0.0001). Multivariate analysis revealed that a abnormal scan was the most important independent predictor of hard or total cardiac events. Event rates increased according to myocardial perfusion scintigraphy (MPS): <1.0% of hard events per year in patients with normal MPS versus 14.3% per year in those with abnormal MPS. (99m)Tc-sestamibi SPECT was demonstrated to be a powerful tool for the prognostic evaluation of elderly patients with suspected CAD.