Certain epidemiological and experimental studies suggest that n-3 fatty acids and folate can reduce blood pressure (BP). We investigated the effect of a daily supplementation with dietary doses of B-vitamins or n-3 fatty acids for 5 years on BP in patients with a history of CVD who participated in the Supplémentation en Folates et Omega-3 trial. The patients (n 2501; 1987 men and 514 women) were randomly assigned in a 2 × 2 factorial design to one of four groups: B-vitamins (5-methyl-THF (560 μg); vitamin B6 (3 mg) and vitamin B12 (20 μg)) and a placebo capsule for n-3 fatty acids; n-3 fatty acids (600 mg of EPA and DHA at a ratio of 2:1) and a placebo capsule for B-vitamins; both B-vitamins and n-3 fatty acids; or placebo capsules for both treatments. The patients took two capsules daily in a double-blind manner for a median duration of 4·7 years. At baseline and annual examination for 5 years, the patients underwent a clinical examination where BP and clinical and biological parameters were assessed. No effect of supplementation with either n-3 PUFA or B-vitamins on BP was observed in crude and adjusted multivariate models. Change in BP was not associated with change in homocysteine. In conclusion, the present results do not support the routine use of dietary supplements containing B-vitamins, or of n-3 fatty acids, to reduce BP in people with prior CVD.