The objective of this study was to test prospectively in a population sample whether individuals with impaired heart rate variability (HRV) are at increased risk of developing coronary heart disease (CHD) and of non-CHD mortality and to test whether this relationship is more pronounced among individuals with diabetes. We examined the association between HRV and incident CHD and non-CHD mortality in a cohort of 11,654 men and women aged 45-64 years at intake, from the biracial, population-based Atherosclerosis Risk in Communities Study. Supine, resting, 2-min beat-to-beat heart rate data were collected at the baseline examination. High frequency (HF; 0.15-0.40 Hz) and low frequency (LF; 0.04-0.15 Hz) spectral powers, LF/HF ratio, normalized HF and LF, the standard deviation of all normal R-R intervals (SDNN), and the mean of the sum of the squared differences between adjacent normal R-R intervals (MSSD) were used as the conventional indexes of HRV to measure cardiac autonomic control. From this cohort, 635 cases of incident CHD (including 346 cases of incident myocardial infarction [MI] and 82 cases of fatal CHD), and 623 non-CHD deaths were identified and validated after an average of 8 years of follow-up. Among individuals with diabetes, the multivariable adjusted proportional hazards ratios (95% CI) were 2.03 (1.28-3.23), 1.60 (1.12-2.27), 1.50 (0.65-3.42), and 1.27 (0.84-1.91) for incident MI, incident CHD, fatal CHD, and non-CHD deaths, respectively, comparing the lowest quartile to the upper most three quartiles of HF. A similar pattern of associations was found for LF, SDNN, and MSSD. By contrast, there was no consistent pattern of associations among individuals without diabetes. At the population level, a lower HRV (reflective of impaired cardiac autonomic control) is statistically significantly related to the development of CHD among individuals with diabetes, independent of markers of the duration/severity of the glucose metabolism impairment. These data suggest a contribution of an impaired cardiac autonomic control to the risk of CHD among individuals with diabetes.