Purpose: An arteriovenous fistula (AVF) is the first choice vascular access for hemodialysis. The AVF pathway can be seen as consisting of seven segments: proximal artery, distal artery, arterial collaterals, proximal vein, distal vein, venous collaterals, and the anastomosis. While most studies describe access complications without considering the impact of the anastomosis (7th segment), the present mathematical study investigated the hemodynamic impact of anastomosis size and angle on pressure drop and flow distribution. Methods: A side-to-end AVF model was developed, consisting of an anastomosis with a given cross-sectional area (substudy 1) and angle (substudy 2). Starting from two reference cases (one for each substudy) with fixed flow distribution, pressure drop over the anastomosis was calculated for an arterial inflow in the range 600 to 1200 mL/min. The same reference cases, subsequently with fixed pressure boundary conditions, were further used to assess flow distribution over the proximal vein and distal artery. Results: Pressure drop decreased with a larger anastomosis cross-sectional area and an angle wider than 43, while it was almost stable for smaller angles. Although proximal arterial inflow increased for larger anastomosis areas, the overall flow distribution shifted almost totally to the proximal vein. When the anastomosis angle exceeded 58, the proximal arterial inflow was not sufficient to deliver enough flow, leading to distal arterial flow reversal. Conclusion: Despite the underestimation of the hemodynamic impact of the anastomosis size and angle in the literature, this study showed major influences on the pressure drop over the anastomosis and, with it, on flow distribution towards the arterial and venous outflow. (J Vasc Access 2010; 11: 52-8)