Many studies have shown that ST-segment depression is a strong predictor of poor outcomes in patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACSs); however, lead aVR was not considered in these studies. The present study examined the prognostic usefulness of the 12-lead electrocardiogram in combination with biochemical markers in 333 patients with NSTE-ACS. ST-segment deviation of > or =0.5 mm was considered clinically significant. Coronary angiography was performed a median of 3 days after admission in all patients. The primary end point was the composite of death, myocardial infarction, and urgent revascularization at 90 days. ST-segment elevation in lead aVR (odds ratio 13.8, 95% confidence interval 1.43 to 100.9, p = 0.03) and increased troponin T (odds ratio 7.9, 95% confidence interval 1.22 to 123.8, p = 0.04) were the only independent predictors of restricted events (death or myocardial infarction) at 90 days. ST-segment elevation in lead aVR (odds ratio 12.8, 95% confidence interval 4.80 to 33.9, p < 0.0001) and increased troponin T (odds ratio 2.03, 95% confidence interval 1.20 to 4.29, p = 0.04) were also the only independent predictors of adverse events (death, myocardial infarction, or urgent revascularization) at 90 days. When ST-segment status in lead aVR was combined with troponin T, patients with ST-segment elevation in lead aVR and increased troponin T had the highest rates of left main or 3-vessel coronary disease (62%) and 90-day adverse outcomes (47%). In conclusion, our findings suggest that ST-segment status in lead aVR combined with troponin T on admission is a simple and useful clinical tool for early risk stratification in patients with NSTE-ACS.