Among patients with unstable angina pectoris (UAP), those who have non-ST-elevation acute myocardial infarction (AMI) are at higher risk for subsequent adverse events. To determine predictors of AMI in patients with UAP, we studied consecutive nonreferral patients with UAP or AMI admitted from the emergency department to the intensive care or telemetry units of an urban teaching hospital over 1 year. There were 280 study patients (mean age 66 years, 1/3 women); 24% had AMI at presentation, whereas 76% had UAP without evidence of AMI. Thresholds of > or = 3 involved leads (odds ratio [OR] 3.3; 95% confidence intervals [CI] 1.6 to 6.9) and > or = 0.2 mV (OR 5.1; 95% CI 2.2 to 11.6) of ST depression on the presenting electrocardiogram were strongly associated with AMI. The multivariate predictors of AMI were reported duration of symptoms >4 hours (OR 3.8; 95% CI 1.9 to 7.3), absence of prior revascularization (OR 3.5; 95% CI 1.6 to 7.5), absence of beta-blocker use before presentation (OR 2.8; 95% CI 1.3 to 5.8), and presence of new ST depression (OR 2.8; 95% CI 1.4 to 5.7). Using the 4 multivariate predictors, a prediction rule was developed. The percentages of patients with AMI when 0, 1, 2, 3, or 4 characteristics were present, respectively, were 7%, 6%, 24%, 46%, and 83% (p <0.001). A similar prediction rule developed from the Thrombolysis In Myocardial Ischemia III trial was validated in our cohort. Among patients with UAP, electrocardiographic and clinical variables can help immediately identify those at high risk for AMI at presentation.