The vasa vasorum (VV) of explanted segments of the human great saphenous vein (Vena saphena magna; HGSV), harvested during dissection for coronary bypass grafts or diseased vein segments from the “Salzburger Landesklinikum,” were studied by scanning electron microscopy and three-dimensional morphometry of microvascular corrosion casts. The main objective of this study was to examine the VV’s structural arrangement in order to find the most vital segments of the HGSV and in turn to improve the results of coronary bypass surgeries. The study presents a meticulous analysis of the whole microvascular system of the VV of the HGSV and its three-dimensional arrangement. It is one of the first studies yielding detailed quantitative data on geometry of the VV of the HGSV. A detailed insight into different vascular parameters such as vessel diameter, interbranching, intervascular distances, and branching angles at different levels of the VV’s angioarchitecture and in different parts of the HGSV in health and disease is given. Further, the geometry of bifurcations was examined in order to compute the physiological optimality principles of this delicate vascular system based on its construction, maintenance, and function.