Background Establishment and maintenance of vascular access for hemodialysis is life-sustaining for patients needing renal-replacement therapy. Arteriovenous fistulas (AVFs) are the preferred type of access, but the costs associated with creation and maintenance are poorly characterized, especially with respect to patient characteristics. Methods A prospectively maintained registry has been established at The Mount Sinai Hospital for patients undergoing access procedures since 2007. We studied 163 patients undergoing successfully placed and cannulated AVFs as their first permanent ipsilateral access and for whom 3-year follow-up was available, including 18 patients with failed contralateral AVFs. Records were analyzed for institutional inpatient and outpatient procedures related to access maturation, imaging, catheter-related procedures, and revisions. We determined hospital costs for 3 AVF locations, assessing the contribution of various factors to variation in costs and patency. Results The median first-year cost of patent AVFs was $8,662, with $4,754 attributable to initial creation. For fistulas remaining patent for at least 3 years, median cumulative 36-month costs were $11,639, with $1,343 attributable to imaging and $10,478 to creation and interventions. Fistulas with patent lifetimes of 19–30 months (3.7%) had median cumulative costs of $26,035. Those with patent lifetimes of 6 months or shorter (6.7%) had median cumulative costs of $17,526. Right-sided fistulas were associated with 41% higher 1-year costs and 38% higher 3-year costs when compared with left-sided fistulas. Human Immunodeficiency Virus (HIV) status and prior history of complex contralateral access were also associated with higher 1-year and 3-year costs. Conclusions Hemodialysis access maintenance contributes significantly to the healthcare burden of renal disease. Our data suggest that particular patient characteristics factor into patency and costs. Short-term mounting costs associated with AVF maintenance may portend poor long-term patency. Rising healthcare costs cannot be easily controlled without understanding the clinical factors driving them.