Limited information is available about clinical presentation, degree of atherosclerosis and effect on overall survival in a large series of patients with coronary artery anomalies. From the National Heart, Lung, and Blood Institute Multicenter Coronary Artery Surgery Study (CASS), detailed coding of coronary angiograms was available in 24,959 patients. Of these patients, 73 (0.3%) had major coronary artery anomalies: 70 had one coronary anomaly and 3 had two coronary anomalies. The most common anomaly involved the circumflex coronary artery (60%). In 69% of these, the circumflex artery arose from a separate ostium in the right coronary sinus, and in 31% it originated as a branch of the right coronary artery. The most common anomalous course was anterior or posterior to the great vessels but not between the great vessels. The major exception to this finding was an anomalous right coronary artery; 7 of 15 such arteries coursed between the great vessels. Anomalous circumflex coronary arteries had a significantly greater degree of stenosis than that in nonanomalous arteries in age- and gender-matched control patients (p = 0.02). Despite this difference, at 7 years there was no significant difference in survival by location or degree of stenosis in the anomalous artery.