EPIC-Heart is the cardiovascular component of the European Prospective Investigation into Cancer and Nutrition (EPIC), a multi-centre prospective cohort study investigating the relationship between nutrition and major chronic disease outcomes. Its objective is to advance understanding about the separate and combined influences of lifestyle (especially dietary), environmental, metabolic and genetic factors in the development of cardiovascular diseases by making best possible use of the unusually informative database and biological samples in EPIC. Between 1992 and 2000, 519,978 participants (366,521 women and 153,457 men, mostly aged 35-70 years) in 23 centres in 10 European countries commenced follow-up for cause- specific mortality, cancer incidence and major cardiovascular morbidity. Dietary information was collected with quantitative questionnaires or semi-quantitative food frequency questionnaires, including a 24-h dietary recall sub-study to help calibrate the dietary measurements. Information was collected on physical activity, tobacco smoking, alcohol consumption, occupational history, socio-economic status, and history of previous illnesses. Anthropometric measurements and blood pressure recordings were made in the majority of participants. Blood samples were taken from 385,747 individuals, from which plasma, serum, red cells, and buffy coat fractions were separated and aliquoted for long-term storage. By 2004, an estimated 10,000 incident fatal and non-fatal coronary and stroke events had been recorded. The first cycle of EPIC-Heart analyses will assess associations of coronary mortality with several prominent dietary hypotheses and with established cardiovascular risk factors. Subsequent analyses will extend this approach to non-fatal cardiovascular outcomes and to further dietary, biochemical and genetic factors.