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Background: In the United States, functional stress testing is the primary imaging modality for patients with stable symptoms suspected to represent coronary artery disease (CAD). Coronary computed tomography angiography (CTA) is excellent at identifying anatomic coronary artery disease (CAD). The application of computational fluid dynamics to coronary CTA allows fractional flow reserve (FFR) to be calculated noninvasively (FFR CT ). The relationship of noninvasive stress testing to coronary CTA and FFR CT in real-world clinical practice has not been studied., Methods: We evaluated 206 consecutive patients at Loyola University Chicago with suspected CAD who underwent noninvasive stress testing followed by coronary CTA and FFR CT when indicated. Patients were categorized by stress test results (positive, negative, indeterminate, and equivocal). Duke treadmill score (DTS), METS, exercise duration, and chest pain with exercise were analyzed. Lesions ≥ 50%stenosis were considered positive by coronary CTA. FFR CT < 0.80 was considered diagnostic of ischemia., Results: Two hundred and six patients had paired noninvasive stress test and coronary CTA/FFR CT results. The median time from stress test to coronary CTA was 49 days. Average patient age was 60.3 years, and 42% were male. Of the 206 stress tests, 75% were exercise (70% echocardiographic, 26% nuclear, and 4% EKG). There were no associations of stress test results with CAD > 50% or FFR CT < 0.80 ( p = 0.927 and p = 0.910, respectively). Of those with a positive stress test, only 30% (3/10) had CAD > 50% and only 50% (5/10) had FFR CT < 0.80. Chest pain with exercise did not correlate with CAD > 50% or FFR CT < 0.80 ( p = 0.66 and p = 0.12, respectively). There were no significant correlations between METS, DTS, or exercise duration and FFR CT ( r = 0.093, p = 0.274; r = 0.012, p = 0.883; and r = 0.034, p = 0.680; respectively)., Conclusion: Noninvasive stress testing, functional capacity, chest pain with exercise, and DTS are not associated with anatomic or functional CAD using a diagnostic strategy of coronary CTA and FFR CT ., Competing Interests: Dr. Nieman has received unrestricted institutional research grants from Siemens, Bayer, GE, and HeartFlow. Dr. Pontone is a consultant for GE Healthcare and has received research grants from GE Healthcare and Heartflow. Dr. Leipsic is a consultant to HeartFlow. Dr. Rabbat is a consultant to HeartFlow., (Copyright © 2021 Demetrios Doukas et al.)