The present study examined the interaction between vital exhaustion and cardiac reactivity and recovery on preclinical atherosclerosis assessed by carotid intima-media thickness (IMT) in young men and women. We measured heart rate (HR), respiratory sinus arrhythmia (RSA), and pre-ejection period (PEP) in response to mental arithmetic and speech tasks. Vital exhaustion and carotid IMT were also measured. Significant associations were observed for men aged 28-37 years, but not for men aged 22-25 years, nor for women in these age groups. It was shown that, among highly exhausted men in the older age group, lower HR reactivity was related to greater IMT. Our results also imply that, among non-exhausted men in this age group, slow HR and RSA recovery after acute stress predicted higher IMT. These results suggest that long-term stress as assessed by vital exhaustion is a risk only if it has resulted in ineffective cardiac stress reactivity. Autonomic imbalance resulting from chronic stress may be the common mechanism linking vital exhaustion and cardiac responsiveness to an increased risk of atherosclerosis.