Endothelial dysfunction and autonomic nervous system imbalance are both risk markers of atherosclerotic vascular damage. The relationship between these 2 factors, however, has not been clarified concisely.Flow-mediated dilation (FMD) was measured in 47 patients with ischemic heart disease (IHD; mean age, 68.1±7.1 years) using an ultrasound semi-automatic measuring system (UNEXEF18G), and autonomic nervous system activity was evaluated by simultaneous measurements of heart rate variability. FMD was significantly correlated with standard deviation of normal-to-normal beats (r=0.33, P=0.022) and the power ratio of low-frequency power to high-frequency power (LF/HF; r=-0.38, P=0.0087). Furthermore, multiple regression analysis indicated that LF/HF was the most important predictor of the magnitude of FMD. This interaction was severely blunted by β-blockers and the presence of diabetes. Moreover, standardized FMD according to autonomic nervous system activity was a better predictor of future cardiovascular events than FMD. Subjects with cardiovascular events had a significantly smaller corrected FMD (event (+), 3.62±0.41; event (-), 5.10±2.35; P=0.001), and the higher corrected FMD was associated with longer event-free survival.Autonomic nervous system activity is an important regulatory factor of FMD in subjects with IHD. Assessment of this interaction can help provide more accurate risk stratification of subjects with IHD.