Background. The safe development of minimally invasive coronary artery bypass operations might require alternatives to conventional suture-based anastomotic techniques. In this setting, nonpenetrating stapling is an attractive option because of its simplicity of use and potential for improved endothelial preservation. Methods and Results. In the experimental part of this study, porcine internal mammary arteries were anastomosed to left anterior descending coronary arteries using either an 8-0 polypropylene running suture or nonpenetrating microclips (7 anastomoses in each group). The endothelium-dependent relaxations to bradykinin of the arterial rings bearing the anastomosis and of noninstrumented rings were compared in organ chamber experiments. There were no significant differences in maximal relaxations (mean ± SEM) between the microclipped and sutured anastomoses (81% ± 7% versus 74% ± 10%), which were both significantly lower than those of control coronary rings (98% ± 2%, p = 0.001 versus the two anastomosed groups). Histologic examination showed a comparable preservation of the coronary and graft endothelium with both techniques. The clinical part of the study comprised 7 patients in whom the left internal mammary artery was conventionally sutured to the left anterior descending whereas 13 saphenous vein grafts were anastomosed to their target vessels by nonpenetrating staples. There were no clip-related complications. An angiographic assessment of the venous grafts was performed within 10 days postoperatively in all patients. One graft is presumably occluded. The 12 remaining conduits were patent with stapled anastomoses featuring a widely open 'shark-mouth' configuration. Conclusions. These preliminary data suggest that nonpenetrating stapling is an easy-to-use technique that competes well with conventional suturing, at least in terms of immediate results. Further studies are warranted to better define its potential place within the armamentarium of minimally invasive coronary artery bypass techniques.