BACKGROUND: Elevated homocysteine levels have been associated with a higher risk of cardiovascular disease. Because folate intake can reduce homocysteine levels, we investigated the association between dietary folate intake and nonfatal myocardial infarction. METHODS: We conducted a case-control study in three tertiary hospitals of Pamplona, Spain, between 1999 and 2001. Study physicians enrolled 171 patients less than 80 years of age with a first nonfatal myocardial infarction and 171 control patients matched by age, sex, hospital and calendar month. We excluded patients with any prior major cardiovascular disease. Participants were interviewed about medical factors and life-style and completed a food frequency questionnaire previously validated in Spain. We calculated energy-adjusted intakes of folate and estimated relative risks (RRs) of myocardial infarction and 95% confidence intervals (CIs) using conditional logistic regression. Relative risks were adjusted for conventional risk factors. RESULTS: Only 6% of participants were taking vitamin supplements. The main sources of folate were green leafy vegetables, green beans, oranges, peppers and lettuces. The estimated matched RR of myocardial infarction for the top three quartiles of folate intake (, above 340 microg/day) was 0.57 (CI = 0.35-0.94), compared with the lowest quartile of intake. The multivariate adjusted RR was 0.51 (CI = 0.24-1.06). There was no apparent dose effect above this threshold. CONCLUSIONS: Our results in a Mediterranean population with natural plant foods as the main source of folate provide further evidence to support the hypothesis that dietary folate intake may be an independent protective factor for myocardial infarction. The magnitude of the effect, its biological plausibility, and the consistency across studies offer support for a causal association.