Background: Although exercise stress electrocardiography (ECG) is a popular tool for detecting coronary artery disease (CAD), the induced ST-depression without coronary artery stenosis (FST) remains a challenge for accurate diagnosis. Exercise-induced ST depression is related to poor prognosis even in non-obstructive disease; however, its determinants have not been fully defined. We sought to investigate whether ventriculo-vascular interactional indexes such as arterial stiffness index, exercise hemodynamic parameters and echocardiographic left ventricular (LV) functional parameters were related to FST. Methods: In the current study, 609 participants who underwent both supine bicycle exercise echocardiography and brachial-ankle pulse wave velocity (baPWV) measurement without exercise-induced regional wall motion abnormalities (RWMA) were analyzed. Referral reasons for stress test were CAD detection or evaluation of patency of previous revascularization. Stepwise graded supine bicycle exercise was performed with simultaneous ECG recording and echocardiography after full conventional resting echocardiography. The FST was defined as newly developed >1 mm ST depression without RWMA during exercise. Results: The median age of the study participants was 65 (59.0–70.5) years, and 222 (37%) patients were women. Among them, 103 (17%) patients showed FST during the exercise or recovery phase. The prevalence of FST did not differ between sexes. Older age, higher pulmonary arterial systolic pressure (PASP), left atrial volume index, baPWV and ankle brachial index at rest and hypertensive response, higher heart rate and rate-pressure product at peak exercise were significantly associated with FST. In multivariate analysis, higher peak heart rate, PASP, and baPWV were independently related to FST. Conclusions: Stress-induced RWMA in addition to ECG should be evaluated to detect CAD in patients with higher baPWV and PASP. FST might be linked to subclinical myocardial ischemia through arterial stiffness and diastolic dysfunction.