Native cephalic vein remains the superior dialysis conduit, even thirty years after it was first described. However, up to 37% of hemodialysis patients develop progressive stenosis in the venous circuit of arterio-venous fistula (AVF), which may later cause thrombosis and occlusion. To study the pre-existing morphological changes in the wall of the cephalic vein before AVF construction, we collected 23 cephalic vein specimens from 3 normal, young trauma and twenty renal failure patients. The samples were collected at the time of vascular repair in the first group and AVF construction in the second group. Sections were prepared and stained for both light and transmission electron microscopy (TEM) examination. Compared with normal cephalic vein, all pre-access cephalic veins showed thickening of the wall and intimal hyperplasia. Other changes were loss of internal elastic lamina in 9 (45%) patients, loss of endothelial cell layer in 6 (30%), inflammatory cell infiltration of the wall in 5 (25%), mural calcification in 3 (15%) and telangiectasia in 2 (10%). Other ultrastructural changes observed were intimal hypertrophy, degeneration and loss of the endothelial cells, degeneration and fraying of smooth muscle cells (SMCs) and loss of wall components into the lumen. In conclusion, most of the apparently normal cephalic veins of renal failure patients showed morphological abnormalities at the time of AVF construction, which may well influence the outcome of shunts in terms of future stenosis and failure. It seems likely that the later development of AVF stenosis may be the result of pre-existing disease rather than the direct insult of arterialization.