We investigated the relationship between clinical, electrocardiographic and angiographic characteristics with development of refractory angina and acute myocardial infarction (AMI) in 976 consecutive patients with unstable angina (UA). AMI occurred in 63 (6%) and recurrent angina in 384 (39%), 201 of whom had >2 episodes (refractory, 21%). Patients with AMI were older (P<0.001) and had a higher rate of smoking (P<0.02), previous cerebrovascular accident (P<0.02), abnormal ST segment on admission (P<0.002), refractory angina (P<0.001) and multivessel disease (P<0.005) than those without AMI. Patients with refractory angina were older (P<0.001) and showed a higher incidence of abnormal ST segment on admission (P<0.001) and multivessel disease (P<0.001) than those without. A multivariate analysis, however, showed that refractory angina (P<0.0001), and multivessel disease (P<0.001) were the strongest predictors of AMI while age and multivessel disease were the strongest predictors of refractory angina (P<0.003). Thus, multivessel disease was the most frequent substrate of refractory angina and AMI in patients with UA. These findings may suggest that significant coronary stenosis in non-culprit arteries may facilitate recurrence of ischemia/AMI perhaps by reacting in concert with the culprit lesion and causing a further reduction of the ischemic threshold.