Many patients presenting to the emergency department with suspected acute myocardial infarction have an initial electrocardiogram (ECG) non-diagnostic for acute injury or ischemia. Continuous ST segment monitoring devices have been used by physicians in the past to diagnose ischemia in the ambulatory outpatient population and to identify coronary occlusion in postthrombolytic and postsurgical patients. We report three patients with suspected acute myocardial infarction who underwent real-time continuous 12-lead ST segment monitoring with frequent serial ECGs on a microprocessor-controlled device during their initial emergency department evaluation. Continuous 12-lead ECG monitoring revealed significant changes on the ECG in all three cases presented, with a resultant change in emergency department therapy. Interestingly, all of these patients had significant ECG changes in the absence of recurrence of chest pain. We believe real-time continuous 12-lead ST segment monitoring with frequent serial ECGs can identify patients with an initially nondiagnostic or atypical ECG who may benefit from early interventional therapy.