Autonomic imbalance, a feature of both diabetes and hypertension, may contribute to adverse cardiovascular outcomes. In animal models, sympathetic nerve activity contributes to renal damage but the extent to which autonomic dysfunction precedes the development of CKD and ESRD in humans is unknown. We measured resting heart rate and heart rate variability in 13,241 adults (45- to 64-years old) followed for a median of 16 years in the Atherosclerosis Risk in Communities (ARIC) Study. We examined heart rate parameters by quartiles, defining those in the lowest quartile (by time and frequency domain measures separately) as the risk group of interest. We identified 199 cases of incident ESRD and 541 patients with CKD-related hospitalizations; higher resting heart rate and lower heart rate variability associated with both outcomes. The fully adjusted hazard ratios for ESRD were 1.98 (95% confidence interval [CI] 1.45 to 2.70) among those in the highest heart rate quartile and 1.56 (95% CI 1.14 to 2.14) for high-frequency power. Other time and frequency domain measures were similarly and significantly associated with ESRD and CKD-related hospitalizations. These results suggest that autonomic dysfunction may be an important risk factor for ESRD and CKD-related hospitalizations and call for further studies to define the mechanisms that underlie these associations.