Intimal hyperplasia and stenosis are often cited as causes of arteriovenous fistulamaturation failure, but definitive evidence is lacking. We examined the associations among preexisting venous intimal hyperplasia, fistula venous stenosis after creation, and clinical maturation failure. The Hemodialysis Fistula Maturation Study prospectively observed 602 men and women through arteriovenous fistula creation surgery and their postoperative course. A segmentof the veinused to create thefistula was collected intraoperatively for histomorphometric examination. Onultrasoundsperformed1day and2 and6 weeksafterfistula creation,weassessedfistula venous stenosis using pre-specified criteria on the basis of ratios of luminal diameters and peak blood flowvelocities at certain locations along the vessel. We determined fistula clinical maturation using criteria for usability during dialysis. Preexisting venous intimal hyperplasia, expressed per 10% increase in a hyperplasia index (range of 0%-100%), modestly associated with lower fistula blood flow rate (relative change, 22.5%; 95% confidence interval [95% CI], 24.6% to20.4%; P=0.02) at 6 weeks but did not significantly associate with stenosis (odds ratio [OR], 1.07; 95% CI, 1.00 to 1.16; P=0.07) at 6 weeks or failure to mature clinically without procedural assistance (OR, 1.07; 95% CI, 0.99 to 1.15;P=0.07). Fistula venous stenosis at 6weeks associatedwithmaturation failure (OR, 1.98;95%CI, 1.25 to3.12; P=0.004) after controlling for case mix factors, dialysis status, and fistula location. These findings suggest that postoperative fistula venous stenosis associates with fistula maturation failure. Preoperative venous hyperplasia may associate with maturation failure but if so, only modestly.