Background: Stress experienced during childhood or adulthood has been associated with cardiovascular disease (CVD), but it is not clear whether associations are already prevalent on a subclinical cardiovascular level. This study investigates associations between indicators of life stress and subclinical CVD, and whether these are mediated by depression and anxiety. Methods: Subjects were 650 participants of the Netherlands Study of Depression and Anxiety, aged 20-66. years, with or without (27.5%) depressive and anxiety disorders. Life stress included childhood trauma, negative life events and recently experienced daily hassles or job strain. Subclinical CVD was measured as 1) carotid atherosclerosis (intima-media thickness and the presence of plaques) using B-mode ultrasonography, and 2) central arterial stiffness (heart rate normalized augmentation index) using calibrated radial applanation tonometry. Results: Increased central arterial stiffness was shown in subjects who had experienced childhood trauma (per SD increase: β= .07; p= .01), or reported recently experienced daily hassles (per SD increase: β= .06; p= .02), negative life events (per SD increase: β= .05; p= .03), or job strain (high versus low: β= .09; p= .01). Associations between life stress and arterial stiffness appeared to be partly mediated by severity of depressive and anxiety symptoms. No significant associations were found for childhood life events, nor between indicators of life stress and carotid atherosclerosis. Conclusions: Childhood trauma and recent life stress were associated with increased central arterial stiffness. This suggests that life stress - partly via depression and anxiety - might enhance the development and progression of CVD.