BACKGROUND AND OBJECTIVES: Treadmill exercise stress echocardiography (TSE) has superior diagnostic accuracy than exercise electrocardiography (ECG). The objectives of the study are 1) to define the diagnostic accuracy and safety of TSE in patients without a history of coronary artery disease (CAD), 2) to identify the clinical characteristics that predict positive TSE results and 3) to assess the differential predictive value between TSE and concomitant exercise ECG in a Korean population. SUBJECTS AND METHODS: A total of 1,287 patients among 1,500 consecutive patients with no prior history of CAD and who were referred for TSE during a 4-year 3-month period were enrolled. RESULTS: Of the 1,287 patients, 95 (7.4%) showed positive TSE results (newly developed regional wall motion abnormality). Among the 154 patients with coronary angiography, 94 patients (61%) showed significant CAD (30 of 77 patients with negative TSE results and 64 of 77 patients with positive TSE results). The TSE positive population had more cardiovascular risk factors and showed a higher Duke treadmill score and wall motion score index than the TSE negative group. TSE showed relatively good sensitivity (68%), specificity (78%) and positive and negative predictive values (83% and 61%, respectively), and TSE also had higher diagnostic accuracy than concomitant exercise ECG (72% vs. 64%, respectively). CONCLUSION: TSE is safe and offers greater diagnostic power for CAD than exercise ECG in Korean population without a history of CAD. Its prognostic value in this population needs to be confirmed in a larger prospective study.