The aim of this study was to assess the diagnostic and prognostic value of the presence and characteristics of ischemic electrocardiographic (ECG) changes during dipyridamole stress echocardiography. The ECG response in 178 patients with echocardiographic evidence of myocardial ischemia during dipyridamole stress testing was analyzed. ECG changes occurred in 105 patients (59%). Patients with ECG changes had a higher incidence of echocardiographic signs of ischemia at a low dose than patients with an unchanged electrocardiogram (50% vs 23%; p = 0.0002). Three-vessel and/or left main coronary artery disease (CAD) was found in 41% of patients with and in 21% of patients without ECG changes (p = 0.029). During follow-up (33 +/- 19 months), 30 cardiac events occurred: 10 deaths, 6 infarctions, and 14 unstable anginas. Coronary revascularization was performed in 48 patients with and in 17 patients without ECG changes (p = 0.0022). The univariate predictors of cardiac events were: presence of ischemia in > or =4 ECG leads (p = 0.0004), echocardiographic evidence of ischemia at a low dose (p = 0.0062), ST-segment shift on precordial leads (p = 0.0094), family history of CAD (p = 0.0115), coexistence of > or =3 cardiovascular risk factors (p = 0.0156), ST-segment depression (p = 0.0172), and ECG changes during testing (p = 0.0335). At Cox analysis, occurrence of ischemia at a low dose (odds ratio 3.0; 95% confidence interval 1.3 to 6.8) and the presence of ischemia in > or =4 ECG leads (odds ratio 3.5; 95% confidence interval 1.3 to 9.3) had an independent prognostic importance. In conclusion, the presence and characteristics of ischemic ECG changes are associated with more extensive CAD and worse prognostic outlook than are echocardiographic changes alone during dipyridamole stress echocardiography.