BACKGROUND Exercise (99m)Tc-tetrofosmin single-photon emission computed tomography (SPECT) is a useful tool for short- and medium-term risk stratifications. Currently, the long-term prognostic application of this technique has not been evaluated. RESULTS Exercise (99m)Tc-tetrofosmin was performed in 655 consecutive patients. Ten patients who underwent revascularization <60 days after nuclear testing were excluded from the analysis. The present data are based on 638 patients with complete follow-up. An abnormal SPECT study was defined as the presence of fixed and/or reversible perfusion defects. End points were cardiac death, nonfatal infarction, and late coronary revascularization. A total of 344 (54%) patients had an abnormal SPECT study. Perfusion defects included fixed defects alone in 186 patients (29%) and reversible defects in 158 (25%) patients. During a mean follow-up of 11.0 ± 3.3 years, 174 (27%) patients died (all-cause mortality). Nonfatal myocardial infarction occurred in 76 (12%) patients, and late coronary revascularization was performed in 194 (30%) patients. Univariable and multivariable Cox proportional hazard regression analyses showed that exercise (99m)Tc-tetrofosmin SPECT provided prognostic information incremental to clinical data and exercise test data. Patients with a normal SPECT had a relatively favorable long-term prognosis, in contrast to patients with an abnormal study who had a significantly increased risk of cardiac events. The SPECT parameters abnormal scan, reversible defect, and summed rest score were strong predictors of long-term outcome. CONCLUSIONS Exercise (99m)Tc-tetrofosmin myocardial perfusion SPECT has an incremental long-term prognostic value over clinical and stress test parameters for the prediction of major adverse cardiac events.