Occlusion of coronary arteries during off-pump coronary bypass operations bears the potential for endothelial injury. The aim of this study was to elucidate the effects of hemostatic devices on the beating heart in human coronaries by means of scanning electron microscopy. The coronary arteries of 9 patients with dilated cardiomyopathy and 13 with ischemic heart disease undergoing heart transplantation were handled with intracoronary shunts as well as external snaring techniques on a beating heart, after cannulation but before starting cardiopulmonary bypass. Adjacent noninstrumented coronary artery segments served as controls. Integrity of endothelial lining was observed with scanning electron microscopy. Nearly all coronary artery segments manipulated with a shunt exhibited a severe injury with extensive endothelial denudation. Endothelial injury was significantly higher after manipulation with intracoronary shunts compared with external occlusion devices (p < 0.001) or control specimens (p < 0.001). Plaque rupture was apparent in 3 samples. Manipulation of human coronary arteries during off-pump operations leads to endothelial denudation and plaque rupture. From this investigation we conclude that insertion of intracoronary shunts during beating heart operations leads to severe endothelial denudation in human coronary arteries. We therefore recommend using shunts selectively in cases where critical ischemia or technical difficulties due to anatomic conditions are expected during anastomosis. The clinical significance of these structural damages has to be further investigated with clinical trials.