PURPOSE: The purpose of this study was to estimate the heart rate variability (HRV)-related lifetime cardiovascular disease (CVD) risk. METHODS: We followed 9744 participants without baseline CVD and used a life-table approach to estimate lifetime CVD risk (coronary heart disease, heart failure, and stroke) from 45 through 85 years according to several HRV measures (the SD of RR intervals [SD(NN)], the root mean square of successive differences of successive RR intervals, the mean of all normal RR intervals [mean(NN)], low-frequency [LF] and high-frequency [HF] power, and the LF/HF ratio). RESULTS: During 192,110 person-years of follow-up, we documented 2856 CVD events. Cox regression analyses with the false discovery rate method correction showed independent associations of SD(NN), mean(NN), LF, and LF/HF in women with CVD. Lifetime CVD risks in the lowest compared with the highest tertile were significantly increased in men for LF/HF (51.3% [95% confidence interval, 47.3-54.7] vs. 43.9% [40.1-47.2]), and in women for SD(NN) (39.4% [36.0-43.0] vs. 29.9% [26.3-33.0]), mean(NN) (39.3% [35.7-42.7] vs. 28.9% [25.7-31.7]), LF (39.4% [35.9-43.0] vs. 30.0% [26.2-33.2]), and LF/HF (37.6% [33.9-40.9] vs. 30.0% [26.8-32.7]). CONCLUSIONS: Greater HRV was modestly associated with lower lifetime CVD risk.