The lipophilic index (LI), a mean measure of fatty acid melting points, has been proposed to capture overall fatty acid profile and may play an important role in the etiology of coronary heart disease. We aimed to determine the association between LI in diet and in adipose tissue and metabolic risk factors for myocardial infarction (MI) and risk of MI. We used a population-based, matched case-control study of nonfatal first acute MI conducted in Costa Rica between 1994 and 2004, with 1,627 case-control pairs. The LI is defined as the mean of the melting points of specific fatty acids in diet or adipose tissue. LIs in diet and adipose tissue were significantly associated with higher plasma triglyceride concentrations, low-density lipoprotein cholesterol concentrations, and low-density:high-density lipoprotein cholesterol ratio. Comparing extreme quintiles for the LI in diet or adipose tissue, the odds ratios for MI were 1.57 (95% confidence interval: 1.22, 2.02; P for trend < 0.001) for dietary LI and 1.30 (95% confidence interval: 1.00, 1.69; P for trend = 0.02) for adipose tissue LI in the multivariable models. We hypothesize that a higher LI in diet and in adipose tissue represents decreased fatty acid fluidity and could play an important role in the etiology of coronary heart disease.