Background: Heart disease remains the leading cause of morbidity and mortality worldwide. Typical symptoms of heart disease are lacking in nearly one-third of patients with acute myocardial infarction (AMI). Simplified ECG assessment via lead I by various handheld and smartphone-based electrocardiogram (ECG) devices may be used for rapid screening without the traditional delays, privacy concerns, or costs of 12-lead ECG recording in patients who are asymptomatic or have atypical symptoms. The purpose of this DNP project was to compare ECG data from lead I to the standard 12-lead ECG to determine its potential efficacy as an early screening tool for AMI. Methods: This project compared ECGs in 84 patients with cardiac diagnoses, 66 (78.6%) had acute myocardial infarction with abnormal 12-lead ECGs and 18 (22.6 %) were without AMI or abnormal findings on the standard 12-lead ECG. ST-segment and T-wave amplitude and characteristics were compared between infarction territories. Results: Lead I in those with abnormal ECGs had a mean ST-segment deviation from baseline of 1.0 ± 0.7 mm, which was significantly different than those with normal ECGs (mean 0.1 ± 0.3 mm)(p = .000). The mean T-wave amplitude in patients with abnormal ECGs was 0.7 ± 1.3 mm, which was a significant reduction compared to those with normal ECGs group of 2.2 ± 1.5 mm (p = .000). Conclusion: ST-segment deviations and reduction in T-wave amplitude are significant indicators of acute myocardial infarction in lead I ECG, the same vector used in handheld single-lead ECG devices.