A total of 389 patients with angiographically determined coronary artery disease, who exhibited a complete absence of angina pectoris in the presence of reproducible myocardial ischemia, were studied in a follow-up investigation. After an initial coronary angiogram, anti-ischemic medication was prescribed as treatment. After a mean follow-up time of 4.9 years (maximum 13.4 years) patients were sent a questionnaire that assessed any new development of angina pectoris pain and cardiac events. In 48 of these patients a second angiogram was recorded after a mean period of 4.2 years. Asymptomatic patients had a worse prognosis than an age-adjusted normal population. After 5 and 10 years, 9 and 26% of the patients, respectively, had died, nonfatal cardiac events (myocardial infarction, bypass surgery or percutaneous transluminal coronary angioplasty) occurred after 5 and 10 years in 19 and 46%, respectively. A large number of initially asymptomatic patients developed angina pectoris pain over the follow-up period (34% after 5 years, 58% after 10 years). Novel angina pectoris pain often preceded cardiac events by months to years. Multivariate analysis indicated that vessel disease (p = 0.0001) and degree of ischemia (defined by ST-segment depression free exercise tolerance, p = 0.04) proved to have independent predictive value with respect to mortality rate. Newly developed angina pectoris was associated with an increase in objective signs of myocardial ischemia and a progression in coronary stenosis. The results indicate that patients who originally had myocardial ischemia with a marked absence of pain can develop angina pectoris over the course of years and that newly developed pain often precedes cardiac events.