OBJECTIVE The purpose of this study was to compare in a randomized, prospective, and controlled study, the performance of a multilayered, self-sealing polyurethane vascular access graft (PVAG) and expanded polytetrafluoroethylene (ePTFE) vascular access grafts in hemodialysis applications. Performance measures included graft survival, complications, time to early cannulation, and hemostasis times after cannulation. METHODS A total of 142 patients were randomized equally to receive one of the two grafts after meeting all eligibility requirements. All patients were followed up prospectively to 12 months or to the end of secondary patency. Specifically, this study documented the performance of the PVAG and ePTFE grafts by determining the patencies and complications for both grafts. RESULTS Patient characteristics between the two groups were similar with respect to risk factors and demographic characteristics (P >.05). Life-table patencies from the date of first dialysis were primary patency: PVAG 55% versus ePTFE 47% (6 months) and PVAG 44% versus ePTFE 36% (12 months) and secondary patency: PVAG 87% versus ePTFE 90% (6 months) and PVAG 78% versus ePTFE 80% (12 months). None of these differences were significant (P >.05). Both primary and secondary patencies were also not significantly different when the date of implantation was the starting point. Adverse events and complications were similar for the two groups, except the PVAG group had a higher incidence of technical complications manifested by graft kinking when compared with the control cohort (P <.05). Additionally, there was no significant difference in complication rates between these two groups with regard to infection and bleeding. When the time to hemostasis after cannulation was compared at 5minutes or less, there were more PVAG cannulation sites that achieved hemostasis compared with ePTFE sites, and this difference was significant (P <.0001). When time to first dialysis access was compared between the two grafts, 53.9% of all PVAG grafts were cannulated before 9 days versus none with the ePTFE grafts (P <.001). However, long-term graft survival was not significantly different when PVAG patients were stratified into early (< 9 days) and the late access (9 >/= days) groups (P =.29). CONCLUSIONS The PVAG graft allows for early access without compromising long-term performance. Both PVAG and standard ePTFE grafts have similar long-term outcomes, despite early access with the PVAG vascular access grafts.