Background: Cardiovascular disease is a worldwide great burden on the health care syste early diagnosis and treatment of CAD can reduce the mortality and morbidity. We aimed to determine the association between upright T wave in lead V1 and coronary artery disease (CAD) in patients who presented with chest pain or positive non-invasive tests in emergency department. Methods: In this retrospective cross sectional design we reviewed the clinical and coronary angiography data of patients who had normal ECG. Presence of coronary artery disease was compared between patients with and without upright T waves in V1. Results: Data of 100 patients with upright T wave more than 1.5 mm in V1 was compared with 100 patients with completely normal ECG. Male patients with coronary artery disease (CAD) were dominant in upright T wave group. However, other traditional cardiovascular risk factors were not statistically different between groups. Based on the multivariate logistic regression model and after adjustment for confounding factors (i.e. gender, dyslipidemia and smoking), presence of upright T wave in the V1 and male gender were still associated with greater risk of coronary artery disease, Odds ratio 4.6 CI 95% (3.1 -6.3) and 3.4 CI 95% (2.2 -4.8), respectively. Conclusions: In patients with chest pain and unremarkable ECG, presence of upright T wave in lead V1, is an early diagnostic tool for CAD. Male patients with chest pain and upright T wave in lead V1 probably have significant CAD.