Fixed perfusion abnormalities in patients with known coronary artery disease (CAD) are associated with myocardial damage and adverse outcomes. However, the significance of these abnormalities in patients without known CAD is unclear. The aim of this study was to assess the prognostic significance of fixed versus reversible perfusion abnormalities in patients without known CAD. We studied 327 patients (58 +/- 11 years of age; 215 men) with no history of myocardial infarction or revascularization, who demonstrated myocardial perfusion abnormalities on stress (exercise or dobutamine) sestamibi tomographic imaging. Follow-up end points were all-cause mortality and hard cardiac events (cardiac death and nonfatal myocardial infarction). Myocardial perfusion abnormalities were reversible in 226 patients (69%) and fixed in 101 patients (31%). During a mean follow-up of 7 years, 72 patients (22%) died (cardiac death in 30) and 15 patients had nonfatal myocardial infarctions. The annual mortality rate was higher in patients with fixed abnormalities than in those with reversible abnormalities (4.4% vs 2.7%, p <0.01), whereas the annual hard cardiac event rate was not significantly different between the 2 groups (2.5% vs 2%). In a multivariate analysis model, the summed stress score was an independent predictor of hard cardiac events (risk ratio 1.7, 95% confidence interval 1.3 to 5.4). The presence of a fixed perfusion abnormality was independently associated with an increased risk of death after adjustment for clinical and stress test data and the summed stress score (risk ratio 2.5, 95% confidence interval 1.3 to 3.7). In patients with suspected, but no history of CAD, fixed perfusion abnormalities were associated with a higher risk of death compared with reversible perfusion abnormalities.