Background: The effects of dietary fats on the risk of coronary artery disease (CAD) have traditionally been estimated from their effects on LDL cholesterol. Fats, however, also affect HDL cholesterol, and the ratio of total to HDL cholesterol is a more specific marker of CAD than is LDL cholesterol. Objective: The objective was to evaluate the effects of individual fatty acids on the ratis of total to HDL cholesterol and on serum lipoproteins. Design: We performed a meta-analysis of 60 selected trials and calculated the effects of the amount and type of fat on total:HDL cholesterol and on other lipids. Results: The ratio did not change if carbohydrates replaced saturated fatty acids, but it decreased if cis unsaturated fatty acids replaced saturated fatty acids. The effect on total:HDL cholesterol of replacing trans fatty acids with a mix of carbohydrates and cis unsaturated fatty acids was almost twice as large as that of replacing saturated fatty acids. Lauric acid greatly increased total cholesterol, but much of its effect was on HDL cholesterol. Consequently, oils rich in lauric acid decreased the ratio of total to HDL cholesterol. Myristic and palmitic acids had little effect on the ratio, and stearic acid reduced the ratio slightly. Replacing fats with carbohydrates increased fasting triacylglycerol concentrations. Conclusions: The effects of dietary fats on total:HDL cholesterol may differ markedly from their effects on LDL. The effects of fats on these risk markers should not in themselves be considered to reflect changes in risk but should be confirmed by prospective observational studies or clinical trials. By that standard, risk is reduced most effectively when trans fatty acids and saturated fatty acids are replaced with cis unsaturated fatty acids. The effects of carbohydrates and of lauric acid-rich fats on CAD risk remain uncertain.