This study assessed the effect of ischemia during dobutamine stress echocardiography (DSE) on cardiac mortality in patients with heart failure. We studied 528 patients (62 +/- 11 years of age, 402 men) who had heart failure and previous myocardial infarction or known coronary artery disease and underwent DSE. Ischemia was defined as new or worsening wall motion abnormalities or a biphasic response. End point during follow-up was cardiac death. Mean ejection fraction was 35 +/- 12%. Ischemia was detected in 407 patients (77%). During a mean follow-up of 3.2 +/- 2.4 years, cardiac death occurred in 150 patients (28%). Myocardial revascularization was performed within 4 months after DSE in 117 patients (29%) who had ischemia. Annual rates of cardiac death were 4.8% in patients who did not have ischemia, 5.5% in those who had ischemia and underwent revascularization within 4 months, and 11.8% in those who had ischemia and were not revascularized (p <0.001 vs other groups). In a multivariate analysis model, independent predictors of cardiac death were diabetes (RR 2, 95% confidence interval 1.4 to 2.9), male gender (RR 1.7, 95% confidence interval 1.2 to 3.1), low-dose wall motion score index (RR 1.4, 95% confidence interval 1.2 to 2.6), and ischemia (RR 1.9, 95% confidence interval 1.3 to 3.2). Angina was not predictive of death. In patients who had ischemia, revascularization within 4 months after DSE was associated with decreased risk of cardiac death (RR 0.43, 95% confidence interval 0.3 to 0.8). In conclusion, myocardial ischemia that is detected by DSE is associated with increased risk of cardiac death among patients who have heart failure, after adjustment for left ventricular function. Patients who had ischemia and received revascularization within 4 months had a better survival than did patients who had ischemia and did not receive revascularization. Angina had no effect on prognosis. Therefore, patients who do not have angina should not be considered a lower-risk population if they have inducible ischemia.