Introduction: Clinical outcomes of FFR-guided PCI have been superior to those of angiographically guided PCI, with or without prior cardiac stress testing. Based on these findings, we hypothesized that the accuracy of stress testing is inferior to that of FFR in determining the physiologic significance of angiographic coronary artery disease. Method: To that end, we studied 243 consecutive patients who underwent coronary angiography and FFR assessment between September 2010 and April 2013 at Mayo Clinic, Florida. Out of this group, we excluded 143 patients due to absence of stress testing in the preceding 6 months. We assessed demographics, coronary risk factors, symptoms, stress test variables, angiographic data, and FFR measurements. FFR values ≤0.80 were considered to be positive for ischemia. We evaluated the diagnostic performance of stress testing vs. FFR. Result: Out of the 100 patients included in the study, FFR was measured in the Left Main coronary artery in 3(3%), in the Left Anterior Descending artery (LAD) in 67(67%), in the left circumflex territory in 11(11%), in the Right Coronary Artery (RCA) in 18(18%). The diagnostic performance of stress testing vs. FFR is summarized in the table, with regards to presence of ischemia in any vascular territory and with regards to a specific vascular territory. Conclusion: Compared to FFR, cardiac stress testing has reasonable NPV but poor PPV in determining the presence of absence of overall ischemia in a given patient. Most concerning, however, is that stress testing has poor PPV and NPV when used to determine the site of ischemia in a specific vascular territory.