A ratio that estimates tissue proportions of omega-6 fatty acids (linoleic acid and/or arachidonic acid [AA]) and omega-3 fatty acids (eicosapentaenoic acid [EPA], docosahexaenoic acid [DHA], and/or alpha-linolenic acid) has been proposed as a biomarker of risk for coronary artery disease (CAD). Use of an omega-6/omega-3 fatty acid ratio instead of either fatty acid class alone is based on theoretical reasons and has not been validated. The relationship between risk for CAD events and tissue omega-3 and omega-6 fatty acid composition was evaluated by pooling data from case-control or prospective cohort studies that examined the risk for CAD end points as a function of tissue fatty acid composition. Thirteen studies were included, 11 case-control and 2 prospective cohort studies, and case-control differences in computed averages of several fatty acids and fatty acid ratios were compared. The largest and most consistent difference was for the sum of EPA + DHA (-11% in cases, p = 0.002). Proportions of EPA, DHA, and AA were about 8% lower in cases, but none of these differences was significant. Total omega-3 and omega-6 fatty acids were lower by 7% and 4%, respectively, in cases versus controls, but only the total omega-3 fatty acid difference was significant. The AA/EPA ratio was nonsignificantly lower by 10% in cases. Fatty acid ratios generally failed to distinguish cases from controls, and any discriminatory power they had derived from the omega-3 fatty acid component. Tissue EPA + DHA appears to be the best fatty acid metric for evaluating for CAD risk.