Introduction Contemporary dogma has classically attributed hand dysfunction following hemodialysis arteriovenous fistula (AVF) placement to regional ischemia. We hypothesize that hemodynamic perturbations alone do not entirely explain the postoperative changes in hand function and, furthermore, that various elements of hand function are differentially affected following surgery. Methods Bilateral wrist and digital pressures and upper extremity nerve conduction tests were recorded preoperatively and at 6 weeks and 6 months following upper extremity AVF construction in 46 patients. Concurrently, biomechanical tests were administered to evaluate multiple limb functional domains, including grip strength, dexterity, sensation, and perception of hand function. Results Mean participant age was 59 ± 14 years (75% male), and 48% were on hemodialysis at the time of access placement. Of the participants, 69% had a brachial-based AVF, and the remainder had radial-based accesses. Six weeks following AVF placement, a significant decrease in access-side digital pressures was observed, with only partial recovery at 6 months (P < 0.0001). Grip strength was significantly worse in the access-side limb (P = 0.0003), and the Disability of Arm, Shoulder and Hand (DASH) questionnaire score substantially worsened postoperatively (P = 0.06). Digital sensation and limb dexterity did not differ between limb sides (P > 0.1) or change significantly over time (P > 0.1). Principal component analyses demonstrated that nerve conduction parameters tended to track the biomechanical parameters, yet both were relatively independent of the hemodynamic parameters. Discussion Our findings suggest that ischemia alone does not completely explain access-related hand dysfunction and that future study is needed to elucidate alternative mechanisms.