Objectives: We investigated the relationship between intima-media thickening (IMT) as an expression of preclinical atherosclerosis and coronary risk factors, including the autonomic nervous system and inflammation markers, in depressed subjects free from coronary artery disease. Methods: We studied 391 asymptomatic subjects with a cluster of risk factors, and we evaluated depression using the Beck Depression Inventory. IMT of the common carotid artery was determined by B-mode ultrasound imaging. Traditional risk factors for atherosclerosis were recorded. Markers of inflammation (C-reactive protein, CRP; interleukin 6, IL-6) and heart rate variability (time domain) were determined. Results: A total of 90 (23.0%) subjects showed a depressive symptomatology. The average IMT was increased in depressed subjects (0.87 ± 0.35. mm) at risk for CHD but free from disease as compared to controls (0.77 ± 0.19. mm; p< 0.001). Heart rate variability was reduced in depressed subjects. Levels of SDNN (103 ± 14. ms) and SDANN (93 ± 20. ms) were decreased in depressed subjects as compared to non-depressed subjects (SDNN 113 ± 22. ms and SDANN 108 ± 35. ms; p< 0.001). Subjects with depression had higher CRP (1.14 ± 0.65. mg/dl) and IL-6 (2.00 ± 0.40. pg/ml) than subjects without depression (CRP: 0.79 ± 0.34. mg/dl; IL-6: 1.6 ± 0.6. pg/ml; p< 0.001, respectively). In multivariate analysis, depression was positively correlated with CRP and IL-6 and IMT, and inversely associated with levels of SDANN. Conclusions: IMT is higher in depressed subjects, indicating that atherosclerosis is accelerated in this sub-group of patients. This is mainly due to patho-physiological mechanisms which connect depression and coronary artery disease, such as inflammation and imbalance of the autonomic nervous system.