Background and Objective: The phospholipids fatty acid content of high density lipoprotein (HDL) has recently been found to be related to several important biological functions which may serve as a risk factor for coronary artery disease (CAD). The purpose of this study was to investigate whether fatty acid composition of HDL phospholipids correlates with the presence and severity of coronary artery disease. Materials and Methods: The study population included 117 patients with coronary artery disease which was approved by angiography. The severity of CAD was assessed by the number of arteries (1, 2 or 3) with more than 50% stenosis reported by angiography. The fatty acid composition of HDL phospholipids was determined by gas liquid chromatography. The independence of association between fatty acids and CAD were evaluated by multivariate analyses which included all of the variables associated with the severity of CAD in univariate analysis. Results: These analyses showed that the association of EPA (β= 0.23, P<0.01) and DHA (β= 0.17, P<0.05) with the severity of CAD was inversely and independently significant. Conclusion: Some kinds of polyunsaturated HDL fatty acid contents such as EPA and DHA (omega-3 fatty acids) have adverse association with severity of CAD. Key words: Coronary artery disease, Fatty acids, High-density lipoprotein