Introduction: Upper extremity ischemia in end-stage renal disease (ESRD) has been attributed to steal syndrome from an ipsilateral arteriovenous fistula (AVF). However, the validity of this assumption, as well as the characteristics, risk factors and mortality in these patients has not been fully described. Methods: Patients with ESRD and ischemia of the hand (n=20) are described and compared to a randomly-selected group of patients with ESRD (n=150) with regard to atherosclerotic risk factors, length of time on dialysis, location and function of AVF and mortality. Results: Of patients with upper extremity ischemia, 16 (80%) required amputation, sympathectomy or debridement of one to four digits, with pathology revealing calcific occlusion and tortuosity in all. While 9 patients (45%) developed ischemia ipsilateral to an AVF, 11 (55%) developed ischemia in the contralateral limb. Time from AVF creation to upper extremity ischemia averaged 60.5 months. 13 patients (65%) have died of their disease an average of 16.4 months after diagnosis while another 3 (15%) have required frequent hospitalizations. When compared to ESRD patients without ischemia, study patients were more likely to be diabetic (70% vs. 46.7%, P=0.035) and to have peripheral vascular disease (PVD, 80% vs. 26%, P<0.001) and coronary artery disease (CAD, 65% vs. 41.3%, P=0.033), and tended to initiate dialysis at a younger age (53.2 yrs vs. 58.1 yrs, p=0.07). Surprisingly, there was no difference in hyperlipidemia (10% vs. 19%, P=0.28) and study patients were less likely to be hypertensive (60% vs. 83.3%, P=0.005). While there was no difference in survival at 1, 3, and 5 years after initiation of dialysis, there was a significantly higher overall mortality in the ischemia group (65% vs. 34%, P=0.003). Conclusions: Upper extremity ischemia in patients with ESRD has characteristic pathologic features, often requiring definitive surgical management. Ischemia does not appear to be related to steal syndrome, which would occur soon after creation of an AVF in the ipsilateral limb. Upper extremity ischemia carries a high mortality rate and is associated with diabetes, PVD and CAD, and may be associated with young age at initiation of dialysis. However, it does not appear related to length of time on dialysis, hypertension or hyperlipidemia. Further studies are needed to more fully characterize the etiology of this disease process in order to impact prognosis.