We analyzed the clinical outcomes in 688 patients with isolated stenosis of one major coronary artery. The survival rate among patients with disease of the right coronary artery (RCA) was higher than that among patients with left anterior descending (LAD) or left circumflex coronary artery (LCA) disease. The survival rate among patients in all three anatomic subgroups exceeded 90% at 5 years. The presence of a lesion proximal to the first septal perforator of the LAD was associated with decreased survival compared with the presence of a more distal lesion. For the entire group of one-vessel disease patients, total ischemic events (death and nonfatal infarction) occurred at similar rates regardless of the anatomic location of the lesion. Left ventricular ejection fraction was the baseline descriptor most strongly associated with survival, and the characteristics of the angina had the strongest relationship with nonfatal myocardial infarction. No differences in survival or total cardiac event rates were found with surgical or nonsurgical therapy. The relief of angina was superior with surgical therapy, although the majority of nonsurgically treated patients had significant relief of angina. The survival rate of patients with one-vessel coronary disease is excellent, and the risk of nonfatal infarction is low. Clinical strategies for the care of these patients must consider the long-term clinical course of one-vessel coronary disease.