The purpose of this study is to increase understanding of the prognosis of coronary artery disease (CAD) patients whose anginal symptoms have been removed by medical therapy, and to evaluate the prognostic and clinical significance of silent myocardial ischemia (SMI). Cardiac events including cardiac death, acute myocardial infarction, PTCA/CABG and unstable angina were examined in 253 CAD patients who underwent ambulatory Holter monitoring, treadmill exercise testing and coronary angiography. The subjects were classified into two groups: 93 patients with exertional angina (AP) without previous myocardial infarction and 160 patients with old myocardial infarction (MI). SMI was diagnosed by Holter monitoring. Cox's proportional hazard regression model and the survival curves using the Kaplan-Meier method were used to analyze 9 variables in patients with AP, including Holter monitoring parameters, exercise parameters and angiographic findings, and 12 variables in patients with MI, including the same parameters as in AP patients. The cardiac event rate was 19% in patients with AP and 18% in patients with MI. The independent and common predictors of unfavorable outcome in both groups were severe coronary lesion and SMI. The incidence of SMI was 30% in AP patients and 38% in MI patients, the same incidence as reported in previous studies. The cardiac event rate in patients with SMI was higher than in those without SMI for both groups (28% vs 9% and 32% vs 9%; p less than 0.05). However, the most frequent cardiac event was different in the groups with SMI: PTCA/CABG in AP patients and re-infarction in MI patients. The significant predictors of cardiac events in patients with SMI were severe coronary lesion, short exercise duration, severe asynergy and exercise-induced angina in patients with AP and lower ejection fraction and maximum ST depression on Holter monitoring in patients with MI. In conclusion, it was ascertained that SMI is a significant and independent marker of unfavorable outcome in patients with CAD and that the cardiac event rate in patients with SMI was significantly higher than in those without SMI. However, severe complications such as acute myocardial infarction were more frequent in MI patients than in AP patients. Therefore, it was suggested that the use of re-vascularization procedure (PTCA/CABG) should be considered as soon as possible in patients with SMI, regardless of whether anginal symptoms are present or not.(ABSTRACT TRUNCATED AT 400 WORDS)