Evidence from randomized controlled trials indicates that consumption of trans fatty acids (TFA) leads to harmful changes in serum lipids, systemic inflammation, endothelial function, and, in nonhuman primates, visceral adiposity and insulin resistance. Prospective observational studies demonstrate strong positive associations between TFA consumption and risk of myocardial infarction, coronary heart disease death, and sudden death. Links have also been seen between TFA intake and incidence of diabetes, adiposity, and other chronic conditions. The physiologic effects demonstrated in randomized trials suggest that TFA consumption produces a unique cardiometabolic imprint via pathways linked to the insulin resistance syndrome. The strength and consistency of the evidence for harmful effects of TFA, together with the feasibility of elimination of industrially produced TFA from foods, indicates little reason for continued use of partially hydrogenated oils containing TFA in food preparation and manufacturing. Consumer education regarding the sources and hazards of TFA, combined with voluntary or legislated adoption by restaurants and food manufacturers of alternatives to partially hydrogenated oils, could avert tens of thousands of coronary events each year in the United States and around the world.