OBJECTIVES: Behavioral and psychosocial factors have been gaining increased attention in regard to cardiovascular diseases. We evaluated sleep conditions, cardiac autonomic function, and carotid atherosclerosis in subjects who participated in the Hyogo Sleep Cardio-Autonomic Atherosclerosis (HSCAA) Study. METHODS: This cross-sectional study included 330 serial patients registered in the HSCAA study who were free from past cardiovascular diseases, and prescribing alpha- or beta-blockers. In addition to clinical background and classical cardiovascular risk factors, sleep efficiency, apnea hypopnea index (AHI), awake physical activity, heart rate variability (HRV), carotid intima-media thickness (IMT), presence of plaque and plaque score were determined. RESULTS: Sleep efficiency (r = -0.183) and all HRV parameters (SDNN: r = -0.202; rMSSD: r = -0.234; pNN50: r = -0.277) were significantly (p < 0.01) and negatively associated with IMT, while AHI (r = 0.220, p < 0.001) was positively associated with IMT. Similarly, sleep efficiency (r = -0.129), HRV parameters (SDNN: r = -0.170; rMSSD: r = -0.217; pNN50: r = -0.260) and AHI (r = 0.184) were also significantly (p < 0.05) associated with plaque scores. Multivariate logistic regression analyses showed that rMSSD, but not sleep efficiency or AHI, was significantly associated with carotid plaque (OR 0.74, 95% CI 0.56-0.98, p = 0.037), independent of classical risk factors. The association of rMSSD with carotid plaque remained significant even after adjustment for sleep efficiency or AHI. A comparison of risk factors in specific subgroups showed that the association of lower HRV with carotid plaque was more prominent in patients with cardiovascular risk factors including male gender, hypertension, dyslipidemia and diabetes mellitus. CONCLUSION: Cardiac autonomic nervous dysfunction was independently associated with carotid atherosclerosis, independent of sleep condition. Moreover, that association was more prominent in specific subgroups with cardiovascular risk factors.