Cardiovascular disease is currently the leading cause of death in France. Intake of folate and vitamins B6 and B12 (due to their role in homocysteine metabolism), and of omega-3 polyunsaturated fatty acids (due to their effects on platelet aggregation, lipid metabolism, and arrhythmias) are among the nutritional factors likely to act as protective factors against cardiovascular and cerebrovascular diseases—those for which there is currently the strongest convergence of pathophysiological, clinical, and, above all, epidemiological evidence. While there are numerous observational epidemiological studies, they do not allow us to conclude that a causal link exists. The SU.FO.LOM 3 study is an intervention trial designed to test, in high-risk subjects (secondary prevention trial), the impact of supplementation with folate, vitamins B6 and B12, and/or omega-3 (at doses achievable through dietary advice and fortified foods) on the incidence (or recurrence) of atherothrombotic cardiovascular and cerebrovascular diseases. This is a randomized, double-blind trial involving 3,000 subjects aged 45 to 80 who, within a period of more than 1 month and less than 12 months prior to enrollment, experienced a myocardial infarction, unstable angina, or an ischemic stroke. Supplementation (factorial design) and follow-up will be conducted over a 5-year period.