Heart rate variability (HRV), a measure of autonomic function, is associated with mortality in non-end stage renal disease (ESRD). The purpose of this pilot study was to determine if HRV was predictive of mortality in patients on dialysis and to identify at-risk factors. Patients on chronic hemodialysis (n = 53) were assessed at baseline and again 24 months later. Baseline measures quantified 24-hour HRV, health, depression, and quality of life (QoL). Twenty-four-month data determined mortality. Participants were African American, 49% male, aged 47.8+/-13.3 years, with 62.4+/-60 months of dialysis. Outcomes of 24-hour HRV measures were impaired for all groups. Factors including exercise and smoking were associated with diminished HRV. The low frequency-high frequency ratio was found to be the most influential HRV determinant of death. The ability to identify patients at-risk for death and to prescribe therapy to reduce risk could have significance for the care of patients with ESRD.