Vital exhaustion (VE) and a hypercoagulable state both have been associated with coronary artery disease (CAD). Candidate mechanisms by which VE predicts CAD events are impaired fibrinolysis and inflammatory changes, the latter also affecting hemostasis. We investigated whether VE and inflammation would independently relate to hemostasis. Study participants were 217 (mean age+/-SD, 40+/-9 years) apparently healthy men and women working at an airplane manufacturing plant in Germany who completed the Shortened 9-item VE Maastricht Questionnaire. All subjects had a set of classic cardiovascular risk factors assessed, and plasma levels of fibrin D-dimer, type I plasminogen activator inhibitor (PAI-1) antigen, C-reactive protein (CRP), and tumor necrosis factor (TNF)-alpha were measured. PAI-1 correlated with VE (r=0.18, p=0.009), CRP (r=0.20, p=0.004), and TNF-alpha (r=0.18, p=0.009); D-dimer correlated with CRP (r=0.16, p=0.018). In linear regression analyses, VE and TNF-alpha independently explained 2 and 1%, respectively, of the variance in PAI-1. Our study corroborates previous findings on impaired fibrinolysis in VE. The findings suggest that VE and inflammation may impair fibrinolysis by different pathways, and independently of traditional cardiovascular risk factors.