Both hospital and epidemiological studies have reported elevated plasma fibrinogen levels in patients with intermittent claudication. Fibrinogen levels have also been positively related to the degree of asymptomatic peripheral arterial disease (PAD). In claudicants, raised fibrinogen is predictive of future cardiovascular events, particularly coronary death. These associations between plasma fibrinogen and PAD are independent of diabetes mellitus and serum lipid concentrations. Lifetime cigarette smoking and plasma fibrinogen interact synergistically in their association with PAD. However, most of the increased risk of PAD due to cigarette smoking is not mediated via plasma fibrinogen, and conversely the relationship between fibrinogen and PAD is not wholly dependent on smoking. The association between fibrinogen and PAD is stronger in men than in women, and in women does not occur independently of smoking. When comparing sex differences in a wide range of aetiological factors associated with PAD, plasma fibrinogen is one of the few factors showing a stronger relationship in men than in women, and may be important in explaining sex differences in susceptibility to disease.