Psychosocial factors might mediate their adverse impact on coronary arteries by eliciting a hypercoagulable state via changes in sympathetic nervous system activity. A recent meta-analysis of prospective studies reported an association of the hypercoagulability marker D-dimer with an increased risk for coronary events. This review provides evidence that an elevated plasma D-dimer level is a suitable marker for acute and chronic psychosocial distress. Prospective studies need to show whether stress-related changes in D-dimer may help explain the increased coronary risk with psychosocial distress.