Heart rate fragmentation (HRF) is a type of sinoatrial instability characterized by frequent (often every beat) appearance of peak and valley in R-R interval time series despite that ECG shows sinus rhythm. Differing from conventional heart rate variability (HRV) mediated by fluctuations in cardiac autonomic activity, HRF is thought to generate within the sinoatrial node of the heart. In this study, we examined the prognostic value of HRF in clinical ECG data. We assessed HRF in 24-hr Holter ECGs that were recorded between January and February in 2010 in 198 chronic hemodialysis patients with end-stage renal disease (ESRD). All ECG recordings showed continuous sinus rhythm and HRF was assessed as the percentage of inflection points (PIP) in 24-h R-R interval time series. We assessed the prognostic value of PIP by the proportional hazard regression analysis of all-cause mortality risk. Among 198 patients, 82 (41%) were diabetes. During followed up for 9 years, 81 (41%) died. Univariate regression analysis showed that age, decrease in very-low-frequency HRV components, and increase in PIP were significant predictors of mortality risk (risk ratio, 1.034 [95% CI, 1.012-1.057], P = 0.002). The predictive power of PIP was independent of age (1.026 [1.003-1.050], P = 0.02). PIP is a new ECG maker of mortality risk among ESRD patients on chronic hemodialysis treatment.