The first ecological epidemiological studies revealed the possible preventive role of some foods which contain antioxidant compounds on cardiovascular disease and on some types of cancer. Nevertheless, later further research and the initial population-based supplementary tests at therapeutic doses have rendered contradictory results. To elucidate the cause-effect relationship of the antioxidant nutrients, the SU.VI.MAX study was considered in France. This is a prospective population-based study of randomized, double blind intervention, the prime objective of which is that of evaluating the effectiveness of a combination of antioxidant minerals and vitamins at nutritional dosages on the morbimortality by cancer and ischemic heart disease of a cohort of 12,749 volunteers of both sexes, ranging from 35 to 60 years of age, spread throughout France over an eight-year period. Likewise, an evaluation was also made of the impact of the supplement on the incidence of infectious disease, cataracts, the individual feeling of well-being and the use of health care resources, the biological markers of the vitamin and mineral status, the antioxidant activity, the immune condition and the evolution of the cardiovascular risk factors. The final points of this study are: the overall mortality, the specific mortality by cancer and/or ischemic heart disease, the incidence of cancer (of any type) and the incidence of ischemic heart disease. The assessment tools employed were: a monthly health questionnaire filled out telematically, a yearly clinical or analytical health check-up every other year, as well as the exhaustive monitoring and documentation of the adverse events and serious health problems. To ascertain the eating behavior and the evolution thereof in the individuals comprising the cohort, an eating survey was filled out twice a month. A description is provided of the means and methods employed in this study, the originality and magnitude of which entail unique aspects which serve to remedy some problems of nutritional epidemiology, as well as the strategies employed for maintaining the active collaboration of the cohort and the exhaustive monitoring thereof. Two years into this study, the consolidation of the monitoring organization and the low drop-out rate afford the possibility of anticipating that the SU.VI.MAX study is going to provide some answers of interest with regard to the relationship between antioxidants and good health.