Functional testing is recommended for risk stratification of medically treated patients with unstable angina. Exercise echocardiography is used in this situation, but its safety and prognostic value are not well defined. The objective of this study was to assess the incremental prognostic value of exercise echocardiography in 226 consecutive patients (128 men, age 59+/-13 years) with medically treated unstable angina, who underwent exercise echocardiography from 1991 to 1996. Clinical risk was designated as low in 108 patients, intermediate in 116, and high in 2 patients according to the unstable angina practice guidelines. There were no major complications from the stress tests. The exercise electrocardiogram was nondiagnostic in 57 patients (25%). Ischemia was identified by exercise electrocardiography in 33 patients and exercise echocardiography in 55 patients. Patients were followed for 29+/-18 months. After exclusion of 38 patients who underwent early revascularization, 28 patients had cardiac death, nonfatal infarction, and late (>3 months) revascularization. Ischemia at exercise echocardiography was associated with a 24-month event-free survival of 81%, compared to 95% with negative exercise echocardiography (p=0.02). A positive exercise electrocardiogram was associated with a 24-month event-free survival of 84%, compared to 93% with negative exercise electrocardiograms (p=0.08). In a Cox regression model, event-free survival was predicted by ischemia at exercise echocardiography (relative risk 2.8, confidence interval: 1.3 to 6.3, p=0.05), but not at exercise electrocardiography (relative risk 2.1, confidence interval 0.7 to 5.8, p=0.16).