ABSTRACT End-stage kidney disease is a disease of aging, exacerbated by multiple coexisting health conditions. Nearly 50% of patients initiating chronic hemodialysis for treatment of end-stage kidney disease are 65 years or older. Patients who use central venous catheters for hemodialysis access typically undergo surgical placement of an arteriovenous access—either a fistula or a graft—to reduce the risks of infection, vascular complications and death associated with catheter use. Arteriovenous fistulas have long been considered first-line vascular access option, with grafts as second best. However, several recent studies suggest that grafts may be a better strategy than fistulas for hemodialysis access in older adults. Without evidence from well-powered randomized clinical trials, these studies cannot be integrated into practice. We conducted the first pilot trial (N=46) that revealed the feasibility of enrolling and randomizing older adults to surgical fistula or graft placement, with 89% (20 of 22) of those assigned to fistula and 79% (19 of 24) of those assigned to graft placement undergoing the assigned intervention. Building on this successful pilot, we propose a pragmatic multicenter randomized clinical trial in 262 adults, 65 years of age and older, receiving hemodialysis via catheters. Unbiased, comparative characterization of clinical outcomes and patient views between alternative access strategies will advance the field, for the first time, to evidence-based vascular access care. Our long-term goals are to optimize clinical decisions based on objective, age-specific data while incorporating goals of care and patient preference for vascular access type. The objective of this proposal is to delineate vascular access effects on disease-specific and patient-reported outcomes, using a randomized intervention, at 6 national sites, of surgical fistula versus graft placement in older adults who have end-stage kidney disease and coexisting coronary artery disease, peripheral arterial disease, and/or diabetes mellitus. The overarching hypothesis is that graft placement strategy will yield more dialysis catheter-free days, lower cost, and better patient satisfaction. Our Specific Aims will determine the effects of fistula versus graft vascular access strategy on rates of catheter-free dialysis days and access-related infections and death (Primary Aim), costs associated with vascular access care (Secondary Aim), and patient-reported satisfaction with access-related outcomes (Tertiary Aim). We will also investigate the relationship between preoperative objective and subjective measures of physical function and failure of fistula or graft maturation (Exploratory Aim). Results from this trial could transform the clinical practice by providing high-quality evidence to guide common clinical decisions on dialysis vascular access in older adults—a growing population whose care is complex and costly.