The clinical presentation and prognosis of 1,977 consecutive patients with normal coronary arteries or "insignificant" coronary artery disease (CAD) (no major epicardial artery with 75% or more luminal diameter narrowing) were examined. Compared with patients with significant CAD, these patients had a lower frequency of traditional cardiac risk factors and abnormalities on the rest and exercise electrocardiogram. Cardiac survival was 99% at 5 years of follow-up and 98% at 10 years for patients with normal or insignificantly narrowed coronary arteries. Patients with normal coronary arteries differed from those with insignificant CAD in their myocardial infarction free survival rate: 99% at 5 years and 98% at 10 years for patients with normal coronary arteries, compared with 97% at 5 years and 90% at 10 years for patients with insignificant CAD. A strong relation occurred between the amount of insignificant CAD and follow-up cardiac events (chi 2 = 21.5, p less than 0.0001). Cardiac risk factors were statistically related to the risk of follow-up cardiovascular events when considered alone (chi 2 = 4.93, p = 0.026), but this relation lost significance after adjusting for the effect of coronary anatomy. Patients in both groups continued to have cardiac symptoms that resulted in frequent hospitalizations, medication use and job disability. Almost 50% in any given year of follow-up could not perform activities of high metabolic equivalent requirement and 70% had continuing symptoms of chest discomfort. Although these patients are at low risk of death, many remain functionally impaired for years.