Venous stenosis and occlusion are a major cause of vascular access dysfunction and failure. The HeRO Graft bypasses occlusion and traverses stenosis with outflow directly into the central venous circulation. A randomized, multicenter study was conducted to evaluate the efficacy and safety of the HeRO Graft relative to conventional AV grafts. The design was to enroll 143 patients in a 2:1 randomization ratio between HeRO and conventional AV control groups. Data on 72 subjects (52 HeRO Graft and 20 AV graft controls) were obtained. The HeRO Graft and control cohorts were comparable in baseline characteristics. Adequacy of dialysis, bacteremia rates, and adverse events were consistent between groups. Twelve month Kaplan–Meier estimates for primary and secondary patency rates were 34.8% and 67.6% in the HeRO Graft cohort, and 30.6% and 58.4% in the control cohort. There was no statistical difference in terms of patency between groups. The rates of intervention were 2.2/year for HeRO Graft and 1.6/year for the control (p = 0.100). Median days to loss of secondary patency was 238 for HeRO Graft versus 102 for the control (p = 0.032). The HeRO Graft appears to provide similar patency, adequacy of dialysis, and bacteremia rates to those of conventional AV grafts.