OBJECTIVE: Autonomic dysfunction frequently occurs in the context of Parkinson disease (PD) and may precede onset of motor symptoms. Limited data exist on the prospective association of heart rate variability (HRV), a marker of autonomic function, with PD risk. METHODS: We included 12,162 participants of the Atherosclerosis Risk in Communities study, a community-based cohort, without a diagnosis of PD at baseline (1987-1989) and with available HRV data (mean age = 54 years, 57% women). A 2-minute electrocardiogram was used to measure HRV. Incident PD was identified through 2008 from multiple sources, and adjudicated. Multivariable Cox models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of PD by quartiles of HRV measurements. RESULTS: During a mean follow-up of 18 years, we identified 78 incident PD cases. Lower values of the root mean square of successive differences in normal-to-normal R-R intervals (rMSSD) and standard deviation of normal-to-normal R-R intervals (SDNN), markers of parasympathetic activity and total variability, respectively, were associated with higher PD risk during follow-up. In multivariate models, the HR (95% CI) of PD in the bottom quartiles of rMSSD and SDNN compared to the top quartiles were 2.1 (1.0-4.3) and 2.9 (1.4-6.1), respectively. Other measures of cardiac autonomic function, including mean R-R interval and frequency-domain measurements, were not associated with PD risk. INTERPRETATION: In this prospective cohort, decreased HRV was associated with an increased risk of PD. Assessment of cardiac autonomic function may help identify individuals at risk for PD.