Background: A number of innovative approaches have been investigated for their value in the early detection of acute ischemia or infarction in patients presenting to the emergency department (ED) with chest pain suggestive of a cardiac origin. Prior investigations have demonstrated the utility of adding right precordial and posterior chest leads to the standard 12-lead electrocardiogram (ECG) for identifying right ventricular and posterior wall infarctions in the ED. Hypothesis: To assess the utility of additional ECG leads in low-risk patients presenting to the ED with symptoms suggestive of acute coronary syndromes who are managed in a chest pain evaluation unit (CPEU). Methods: We studied low-risk patients who presented to the ED with chest pain compatible with myocardial ischemia. Low-risk patients were identified by a normal 12-lead ECG, no arrhythmias or hemodynamic instability, and one negative serum cardiac troponin I. Patients were admitted to the CPEU where a 16-lead ECG was recorded by the addition of 2 right-sided precordial leads (V4R, V5R) and 2 posterior leads (V8, V9) to the standard 12-lead ECG. Results: The 16-lead ECG system was applied to 316 consecutive patients. The study group was a middle-aged population with equal numbers of men and women and an average of 2 cardiac risk factors per patient. The 16-lead ECG demonstrated evidence of myocardial injury in only 1 patient and no evidence of ischemia in any of the 316 patients. Conclusion: In patients presenting to the ED with chest pain and evidence of low clinical risk by our criteria, the addition of both right-sided precordial and posterior chest leads to the standard 12-lead ECG did not provide additional information for risk stratification.