Intake of trans fatty acids unfavorably affects blood lipoproteins. As margarines are a major source of trans, claims for the advantages of margarines over butter need to be scrutinized. Here we review dietary trials that directly compared the effects of butter and margarine on blood lipids. We identified 20 studies in which subjects had stable body weights, and margarine and butter were exchanged in the diet at constant energy and fat intake. We calculated the changes in average blood lipid levels between study diets (49 comparisons) as a function of the percentage of calories as margarine substituted for butter. Replacing 10% of calories from butter by hard high-trans stick margarines lowered total serum cholesterol by 0.19, LDL by 0.11, and HDL by 0.02 mmol/l, and did not affect the total/HDL cholesterol ratio. Soft low-trans tub margarines decreased total cholesterol by 0.25 and LDL by 0.20 mmol/l, did not affect HDL, and decreased the total/HDL cholesterol ratio by 0.20. Based on the total/HDL cholesterol ratio, replacement of 30 g of butter per day by soft tub margarines would theoretically predict a reduction in coronary heart disease risk of 10%, while replacement of butter by hard, high-trans margarines would have no effect. Replacing butter by low-trans soft margarines favorably affects the blood lipoprotein profile and may reduce the predicted risk of coronary heart disease, but high-trans hard margarines probably confer no benefit over butter.