This study was designed to evaluate microvascular clip potential for causing changes in vessel-wall tissue and the extent to which this potential is influenced by features of the clip. Light and scanning electron microscopy were used to examine vessel-wall changes after temporary clip occlusion. Vessel patency is shown to be influenced by anastomosis and clip site, changes in occlusion force due to material fatigue are described, and novel clip features to reduce vessel trauma are proposed. Evaluation of mechanical clip properties showed that material fatigue does not lead to relevant loss of precision in alpha-type clips. While the modified clip designed to reduce trauma cannot abolish trauma altogether, it significantly reduces the associated changes and hence the risk of thrombosis. Arteries were more sensitive than veins to clip-induced trauma, with increased occlusion force producing more severe damage than increased clipping time. Maximal changes were seen in the tunica media. These results indicate the paramount importance of applying modest clip pressure commensurate with the requirements of microvascular Surgery.