Background The primary objective of the present study was to determine whether there is an association between the ankle - brachial index (ABI) and the risk factor profile in patients with newly diagnosed peripheral arterial disease (PAD). A secondary objective was to identify the risk factor profile of these patients, and evaluate how well these factors are controlled in the primary care setting. Methods and Results In this cross-sectional study, all new consecutive patients referred by primary care to a vascular surgery outpatient clinic, after diagnosis of PAD was confirmed, were subsequently referred to the Risk Factor Modification Clinic for assessment and management of their risk factors. Patients with intermittent claudication (n=170) (age 68.7±10.6 years; 118 men; ABI 0.65±0.13) were included. In patients not on lipid-lowering drugs, low-density lipoprotein-cholesterol (LDL-C) was inversely correlated with the ABI (r=-0.42, p<0.0001). Also ABI was significantly correlated with serum creatinine (r_s=-0.38, p<0.0001) (and estimated glomerular filtration rate), high-sensitivity C-reactive protein (hsCRP) (r_s=-0.20, p=0.009) and plasma fibrinogen (r_s=-0.18, p=0.018). In stepwise multiple linear regression analysis, hsCRP and creatinine levels and diabetes were independent predictors of ABI (p<0.0001). Only 32.4% of the patients had normal blood pressure and 25.9% had an optimal LDL-C level <2.6 mmol/L (100 mg/dl); 85.3% were ever smokers; 44.1% had diabetes/impaired fasting glucose; 84.7% had hsCRP >3.0 mg/L; 78.8% fibrinogen >3.0 g/L (300 mg/dl); and 68.8% homocysteine >12.0 μmol/L (44.7% >15.0 μmol/L). Conclusions For the first time, a significant inverse correlation between ABI and LDL-C was shown in patients not on lipid-lowering drugs, and also between ABI and creatinine, hsCRP and fibrinogen in all patients, supporting a link between the severity of PAD and atherogenic and inflammatory risk factors. HsCRP, creatinine and diabetes were independently associated with the ABI. Despite the increased vascular risk, PAD remains undertreated in the primary care setting. Increased awareness will overcome this barrier to effective secondary prevention of vascular events. (Circ J 2008; 72: 441 - 448)