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Background: Vascular access (VA) is the lifeline of hemodialysis patients. Although the autonomic nervous system might be associated with VA failure (VAF), it has never been addressed in previous studies. This study aimed to evaluate the predictive values of the heart rate variability (HRV) indices for long-term VA outcomes., Methods: This retrospective study was conducted using a prospectively established cohort enrolling 175 adult chronic hemodialysis patients (100 women, mean age 65.1 ± 12.9 years) from June 2010 to August 2010. Each participant received a series of HRV measurements at enrollment. After a 60-month follow-up period, we retrospectively reviewed all events and therapeutic procedures of the VAs which existed at the enrollment and during the follow-up period., Results: During the 60-month follow-up period, 37 (26.8%) had VAF but 138 (73.2%) didn't. The values of most HRV indices were statistically increased during hemodialysis since initiation in the non-VAF group, but not in the VAF group. Among all participants, the independent indicators for VAF included higher normalized high-frequency (nHF) activity [hazard ratio (HR) 1.04, p = 0.005], lower low-frequency/high-frequency (LF/HF) ratio (HR 0.80, p = 0.015), experience of urokinase therapy (HR 11.18, p = 0.002), percutaneous transluminal angioplasty (HR 2.88, p = 0.003) and surgical thrombectomy (HR 2.36, p = 0.035), as well as higher baseline serum creatinine (HR 1.07, p = 0.027) and potassium level (HR 1.58, p = 0.037). In subgroup analysis, a lower sympathetic activity indicated by lower LF/HF ratio was an independent indicator for VAF (HR 0.61, p = 0.03) for tunneled cuffed catheter, but conversely played a protective role against VAF (HR 1.27, p = 0.002) for arteriovenous fistula., Conclusions: HRV is a useful tool for predicting long-term VAF among hemodialysis patients.