Hemodialysis is a common treatment for approximately 370,000 patients in the United States with end-stage renal disease [1]. To optimize the procedure, the dialysis access site must be easily accessible but must also be able to continuously provide high blood flow rates: >250 mL/min [2]. If there is insufficient blood flow through the access, then the dialysis procedure becomes impractical or ineffective. To provide these features, an arteriovenous (AV) fistula is typically surgically created in the arm: an artery and a vein are anastomosed together, bypassing the high flow resistance of the capillary bed and providing enhanced flow through the artery and into the access vein. Unfortunately, as many as 60% of AV fistulae require an intervention within one year to maintain clinical patency [3,4]. There are two major causes of patency loss: thrombotic occlusion, brought on by aggressive intimal hyperplasia and stenotic lesions, or impaired dilation, whereby impaired venous remodeling does not provide a sufficient flow rate at the access site [2]. In the United States alone, it is estimated that the total expenditures related to access site complications and revisions exceed $2 billion per year [1]. After the creation of the fistula, the vein undergoes a rapid remodeling process, leading to an increase in the diameter of the lumen and increased muscular thickness in the wall, which is a process referred to as vein arterialization [5]. It has long been hypothesized that hemodynamic forces constitute the primary external influence on the remodeling process [6,7]. Since an AV fistula causes a dramatic rise in the flow rate and wall shear stress outside of normal physiological values, it is hypothesized that the vein and artery lumens chronically increase as a way to renormalize the value of the wall shear stress. The remodeling of the vessels has been shown to correlate with the initial time-averaged wall shear stress as evidenced by animal models of AV fistulae [6,7] and ultrasound surveillance in dialysis patients [5,8]. These studies hypothesized that the remodeling stops once the mean wall shear stress in the fistulae reach about 1.5 Pa in the radial artery and about 1.0 Pa in the cephalic vein. The renormalization of shear stress in the fistula vessels has been interpreted as evidence of a “mechanical homeostasis” [9]: the vessels seek to maintain a preferred mechanical state through a process of growth and remodeling. The shear-induced remodeling is widely hypothesized to be regulated in part by the vascular endothelium [10]. Despite the pervasive use of the AV fistula for dialysis access, the mechanisms which drive a fistula to either successful remodeling and patency versus occlusion and failure remain unclear [11]. Even though blood flow is thought to play an important role in fistula remodeling, the characterization of the hemodynamic stresses occurring within fistulae remain ambiguous [12], even within functioning accesses [13]. Characterizing the fistula hemodynamics has been hindered, in part, due to the relative complexity of the flow, including separation, vortex shedding, and swirling flows [14]. In this study, we use 3D ultrasound imaging and computational fluid dynamics to determine the hemodynamics in four mature AV fistulae of hemodialysis patients. The hemodynamic analysis aims to quantify the mechanical stresses occurring due to complex secondary flows. It is important to first characterize the hemodynamics in patent accesses in order to eventually understand the negative influence of hemodynamics in failing accesses [11]. It is furthermore unlikely that effective clinical treatments for fistula maturation will be successful until a more precise characterization of fistula hemodynamics is articulated [10].