Arteriovenous fistula (AVF) failure is mainly due to venous stenosis characterized by significant amount of intima-media thickening (IMT), probably in the presence of negative (inward) remodeling. Our hypothesis is that the longitudinal changes in wall shear stress (WSS) within different configurations of AVF can influence remodeling factors (changes in luminal diameter (ΔDh) and IMT) during its maturation process. Dh is an equivalent diameter for a noncircular conduit. A total of six AVFs with curved (C-AVF; n = 3) and straight (S-AVF; n = 3) configurations were created between the femoral artery and vein of three pigs, bilaterally. CT scans and ultrasounds were utilized to calculate local WSS at 2D (D: days), 7D, and 28D postsurgery. For each AVF, IMT was measured at four regions along the vein using morphometric analyses. At these regions, repeated measurements of WSS and luminal diameter of each AVF were obtained over time. The ΔDh between 7D and 28D was significantly larger for C-AVF than for S-AVF (2.27 ± 0.67 mm vs. 0.02 ± 0.55 mm; p < 0.05). Also, at 28D the amount of IMT in C-AVF (77.46 ± 7.10 units) was significantly greater (p < 0.05) when compared with S-AVF (53.71 ± 8.23 units). These structural changes were accompanied by significantly different gradients of WSS over time (τ′) for C-AVF (−0.56 ± 0.60 dyne/cm2/day) in comparison with S-AVF (0.71 ± 0.39 dyne/cm2/day). Negative τ′ for C-AVF corresponded to reduction in WSS level over time resulting in a physiological level of WSS at 28D (4.08 ± 5.08 dyne/cm2). In contrast, a positive τ′ for S-AVF was associated with the increase in WSS levels over time causing high levels of WSS at 28D (36.68 ± 5.32 dyne/cm2). The decrease in WSS levels for the C-AVF over time was associated with outward remodeling of the venous wall (favorable to maturation). In contrast, for S-AVF, the increase in WSS levels over time was associated with inward remodeling and subsequently, venous stenosis. Thus, temporal gradients of WSS, which could be altered by the surgical configuration of AVF, may provide important information on the remodeling behavior of AVFs. Identification of an optimal AVF configuration, which results in a temporal decrease in WSS and an outward remodeling of the venous wall, may reduce AVF maturation failure.