Antioxidants, particularly carotenoids and tocopherols, may protect against cardiovascular disease. The objective of this study was to determine whether dietary and adipose tissue carotenoids and tocopherols are associated with the risk of myocardial infarction (MI). Cases (n = 1456) of a first acute MI were identified and matched by age, sex, and residence to randomly selected population controls (n = 1456) living in Costa Rica. Carotenoids and tocopherols were measured in adipose tissue using HPLC. Dietary intake was assessed using a validated FFQ. Anthropometrical and lifestyle data were collected using an interviewer-administered questionnaire. Subjects were distributed into quintiles of intake or adipose tissue concentration of carotenoids or tocopherols. The lowest quintile was used as the referent in conditional logistic regression analyses. Adipose tissue beta-carotene showed a significant inverse relation with MI risk; the odds ratio (OR) comparing the highest to the lowest quintile was 0.70 (95% CI: 0.51-0.96, P for trend = 0.02). Intake of fruits and vegetables that are rich in beta-carotene was also inversely associated with the risk of MI (OR = 0.74; CI: 0.54-1.01, P for trend = 0.09). In contrast, lutein + zeaxanthin in adipose tissue (OR = 1.46; CI: 1.05-2.05, P for trend = 0.02) and diet (OR = 1.18; CI: 0.88-1.57, P for trend = 0.02) was positively associated with MI risk. MI risk was not associated with any of the other carotenoids or tocopherols in the diet or adipose tissue. Thus, the inverse association between beta-carotene and MI risk suggests that beta-carotene protects against MI or it is a marker of some protective factor in foods containing beta-carotene. The mechanism underlying the positive association between lutein + zeaxanthin and the risk of MI warrants investigation.