There is growing evidence that fibrin D-dimer is associated with coronary and peripheral atherosclerosis. Using data from the Edinburgh Artery Study, we examined the distribution of fibrin D-dimer in 1592 men and women 55 to 74 years old and assessed its relationship with a range of cardiovascular risk factors. Fibrin D-dimer levels were higher in women than in men (P < or = .05) and increased with age (P < or = .001). Current cigarette smokers had higher levels than ex-smokers, who, in turn, had higher levels than those who had never smoked. On multiple regression analyses with age and plasma fibrinogen as covariates, only lifetime smoking in men and systolic blood pressure in women were independent predictors of fibrin D-dimer levels. Since fibrin D-dimer does not appear to be independently related to many of the common cardiovascular risk factors, it may be a useful index of the thrombotic contribution to arterial disease.