Purpose: Venous stenosis secondary to neointimal hyperplasia is a major etiology of early arteriovenous fistula (AVF) failure. The natural history of AVF failure is likely influenced by progressive vascular insults to the vein prior to and after AVF creation. The main objectives of this study were to (1) provide a histologic and morphometric description of non-chronic kidney disease (CKD), upper extremity vein specimens and (2) perform a morphometric analysis to study venous histology from non-CKD upper extremity veins, veins collected at the time of new vascular access surgery and veins collected from failed stenotic AVFs. Methods: Vein samples from 11 non-CKD deceased donors, 29 subjects receiving new vascular access creation and 20 subjects with stenotic failed AVFs were collected for histologic and morphometric analysis. Results: The mean values of average intima/media thickness ± S.E. from veins collected from non-CKD subjects, subjects receiving new vascular access and subjects with stenotic AVFs were 0.16±0.02, 0.43±0.07 and 3.84±0.55, respectively (p<0.0001). Among donor, non-CKD, vein samples, only diabetes (p=0.0007) was associated with increased average intima/ media thickness. Conclusions: Our results demonstrate a progressively increasing venous neointimal hyperplasia development from the non- CKD period through the period of AVF creation and failure. Vascular injuries from complications of progressive CKD prior to access placement and vascular injuries after vascular access placement may play important roles in these progressive vascular changes, and need to be further elucidated. © 2014 Wichtig Publishing.