A prospective randomized study comparing intensive medical therapy with urgent coronary bypass surgery for the acute management of patients with unstable angina pectoris was carried out by nine cooperating medical centers under the auspices of the National Heart, Lung, and Blood Institute. Between 1972 and 1976, a total of 288 patients were entered into the study. All patients had transient S-T or T wave changes, or both, in the electrocardiogram during pain; 90 percent had pain at rest in the hospital, and 76 percent had multivessel coronary disease. The medically and surgically treated patients were comparable with respect to clinical, electrocardiographic and angiographic characteristics and left ventricular function. During the total study period, the hospital mortality rate was 5 percent in the surgical group and 3 percent in the medical group (difference not significant). The rate of in-hospital myocardial infarction was 17 and 8 percent in the respective groups (P < 0.05). In the last 4 years of the study (1973 to 1976), the hospital mortality rate decreased to 3 percent in the surgical group and to 2 percent in the medical group (difference not significant). During the last 3 years of the study (1974 to 1976), the rate of in-hospital myocardial infarction was 13 percent in the surgical group and 10 percent in the medical group (difference not significant). There were no differences in the subsets of patients with one, two or three vessel disease. In the 1st year after hospital discharge class III or IV angina (New York Heart Association criteria) was more common in medically than in surgically treated patients with one vessel disease (22 percent versus 3 percent, P < 0.05), two vessel disease (40 percent versus 13 percent, P < 0.01) and three vessel disease (40 percent versus 15 percent, P < 0.01). During an average follow-up period of 30 months, 36 percent of the medically treated patients later underwent surgery to relieve unacceptable angina. Late mortality was comparable in the two groups, but the large number of medically treated patients who later underwent surgery prevents definitive conclusions about the relative effect of medical and surgical therapy on long-term mortality. However, the patients who responded to medical therapy did not have a higher late mortality rate than surgical patients. The results indicate that patients with unstable angina pectoris can be managed acutely with intensive medical therapy, including the administration of propranolol and long-acting nitrates in pharmacologic doses, with adequate control of pain in most patients and no increase in early mortality or myocardial infarction rates. Later, elective surgery can be performed with a low risk and good clinical results if the patient's angina fails to respond to intensive medical therapy. © 1978.