BACKGROUND: Olive oil is the main source of dietary lipids in most Mediterranean countries where mortality and incidence rates for coronary heart disease (CHD) are the lowest in Europe. Although international comparisons and mechanistic reasons support the hypothesis that a high olive oil intake may prevent CHD, limited data from studies of individuals are available. METHODS: A hospital-based case-control study was conducted in Pamplona (Spain) recruiting 171 patients (81% males, age <80 years) who suffered their first acute myocardial infarction and 171 age-, gender- and hospital-matched controls (admitted to minor surgery, trauma or urology wards). A validated semi-quantitative food frequency questionnaire (136 items) was used to appraise previous long-term dietary exposures. The same physician conducted the face-to-face interview for each case patient and his/her matched control. Conditional logistic regression modelling was used to take into account potential dietary and non-dietary confounders. RESULTS: The exposure to the upper quintile of energy-adjusted olive oil (median intake: 54 g/day) was associated with a statistically significant 82% relative reduction in the risk of a first myocardial infarction (OR = 0.18; 95% CI : 0.06-0.63) after adjustment for dietary and non-dietary confounders. CONCLUSIONS: Our data suggest that olive oil may reduce the risk of coronary disease. These findings require confirmation in further observational studies and trials.