OBJECTIVE Fractional flow reserve-guided coronary artery bypass grafting is emerging in cardiac surgery, in which the nature (anatomic and functional characteristics) of the target vessel epicardial coronary artery stenosis is important in graft site selection. The nature of the stenosis might determine a different physiologic response to bypass grafting. We report our recent experience using near infrared fluorescence complex angiography and perfusion analysis to identify the nature of stenoses in the target vessel by imaging the physiologic response to grafting. METHODS In 167 patients who underwent consecutive multivessel coronary artery bypass grafting cases (63% off-pump coronary artery bypass grafting) with traditional anatomy-based revascularization, we imaged and analyzed 359 grafts (53% arterial). This platform provides angiographic data of both the target vessel epicardial coronary artery and graft simultaneously (to assess the imaged competitive flow); and because a change in fluorescence intensity is proportional to the change in blood flow and perfusion, the quantified change (if any) in regional myocardial perfusion surrounding the grafted target vessel epicardial coronary artery. RESULTS The patient outcomes in our series were excellent. All 359 grafts were widely patent by angiography, and 24% of the arterial and 22% of the saphenous vein grafts showed no regional myocardial perfusion change in response to bypass grafting. In 165 in situ internal mammary artery grafts to the left anterior descending artery (>70% stenosis), 40 had no change in regional myocardial perfusion, and 32 of the 40 had competitive flow imaged. CONCLUSIONS An important number of angiographically patent bypass grafts demonstrated no change in regional myocardial perfusion, suggesting anatomic, but nonfunctional, stenoses in those target vessel epicardial coronary arteries. In in situ arterial grafts, imaged competitive flow is associated with nonfunctional stenoses in the target vessel epicardial coronary artery. Imaging these physiologic responses to target vessel revascularization might be useful in the emerging fractional flow reserve-guided era.