Background: Atherosclerosis is a systemic disease and patients presenting with atherosclerotic coronary artery disease (CAD) usually have associated vascular disease and the reverse is true. Clinical application of this association in detecting CAD is lacking.Objective: (a) To investigate the relationship between the carotid and femoral atherosclerosis as assessed by ultrasonography, and the severity of coronary atherosclerosis, provided by coronary angiography. (b) To assess the validity and applicability of the new algorithm for detection of significant CAD. Methods: Peripheral arterial duplex evaluation was performed for 97 consecutive patients (65 men and 32 women; mean age 59 4.5 years) undergoing coronary angiography for a variety of indications. Common carotid and common femoral intima media thickness (IMT), carotid total plaques dimension product (PDP) and CARFEM index were determined in all patients. Results: As the number of affected coronary arteries increased, there was a proportional increase in the mean of CCA IMT, total PDP and CARFEM Index (P= .025, < 0.001 and 0.017 respectively ). Sensitivity, specificity, positive and negative predictive values of the proposed algorithm were 90.3% 72%, 90.3% and 72% respectively.The sensitivity and specificity were 93% and 91% respectively in non-diabetics compared to 86.2% and 57% in diabetics; 95% and 90% in women compared to 88% and 60% in men.Conclusion: Carotid and femoral duplex ultrasonography provides a simple and easy non-invasive tool for detection of significant CAD.