A group of 125 patients with unstable angina were studied over a 5-year period to define the incidence of refractory unstable angina in the current era of 5-drug medical therapy with intravenous heparin, aspirin, nitrates, calcium antagonists and beta-blockers. All patients had >20 minutes of chest pain at rest with reversible electrocardiographic changes occurring in the absence of myocardial infarction. Patients were considered refractory only if chest pain continued despite treatment with maximal 5-drug therapy. At the time of transfer to the center, 65 patients continued to have ischemic chest pain at rest and were considered "medically refractory" by their referring physicians. A more aggressive medical regimen was used, and 54 patients (83%) were rendered chest pain-free. Of the 11 truly refractory patients (8.8%), coronary arteriography revealed an increased likelihood of left main or 3-vessel disease (7 of 11 vs 26 of 114; p = 0.01). In-hospital treatment strategies for the 114 patients stabilized with medical therapy included continued medical therapy (n = 37), coronary angioplasty (n = 46) and bypass grafting (n = 31). The rate of myocardial infarction or death in patients managed medically was 3%. Coronary angioplasty in medically stabilized patients was complicated by an abrupt closure rate of 26%, and a 17% rate of myocardial infarction, death or need for emergency bypass grafting. Medically stabilized patients undergoing bypass grafting had a 9% rate of myocardial infarction or death. Unstable angina truly refractory to current, maximal medical therapy is infrequent (8.8%). However, the refractory group is vulnerable to adverse angioplasty results and cardiac events.