The vasa vasorum of skeletonized and nonskeletonized segments of five human great saphenous veins (GSVs), harvested during coronary bypass grafting, were cannulated, rinsed, and injected (casted) with the polymerizing resin Mercox-Cl-2B. After removal of the dry vascular tissue, the casts were examined using scanning electron microscopy. Stereopaired images (tilt angle, 6°) were taken, imported into a 3D morphometry system, and the 3D architecture of the vasa vasorum (arterial and venous vasa as well as capillaries) was studied qualitatively and quantitatively in terms of vasa diameters, intervascular and interbranching distances, and branching angles. Diameters of parent (d 0 ) and large (d 1 ) and small (d 2 ) daughter vessels of arterial and venous bifurcations served to calculate asymmetry ratios (␣) and area ratios (). Additionally, deviations of bifurcations and branching angles from optimal branches were calculated for selected arterial vasa. The arrangement of the vasa vasorum closely followed the longitudinally oriented connective tissue fibers in the adventitia and the circularly arranged smooth muscle cell layers within the outer layers of the media. Venous vasa by far outnumbered arterial vasa. Vasa vasorum changed their course several times in acute angles and revealed numerous circular constrictions, kinks, and outpouchings. Due to their spatial arrangement, the vasa vasorum are prone to tolerate vessel wall distension generated by acute increases in blood pressure or stretching of the vessel without severe impact on vessel functions. Preliminary comparisons of data from the bifurcations of cast arterial vasa vasorum, with calculated optimal bifurcations, do not yet give clear insights into the optimality principle(s) governing the design of arterial vasa vasorum bifurcations of the human GSVs.