AimsScarce data are available on the effect of the traditional Mediterranean diet (TMD) on heart failure biomarkers. We assessed the effect of TMD on biomarkers related to heart failure in a high cardiovascular disease risk population.Methods and ResultsA total of 930 subjects at high cardiovascular risk (420 men and 510 women) were recruited in the framework of a multicentre, randomized, controlled, parallel‐group clinical trial directed at testing the efficacy of the TMD on the primary prevention of cardiovascular disease (The PREDIMED Study). Participants were assigned to a low‐fat diet (control, n = 310) or one of two TMDs [TMD + virgin olive oil (VOO) or TMD + nuts]. Depending on group assignment, participants received free provision of extra‐virgin olive oil, mixed nuts, or small non‐food gifts. After 1 year of intervention, both TMDs decreased plasma N‐terminal pro‐brain natriuretic peptide, with changes reaching significance vs. control group (P < 0.05). Oxidized low‐density lipoprotein decreased in both TMD groups (P < 0.05), the decrease in TMD + VOO group reaching significance vs. changes in control group (P = 0.003). Changes in lipoprotein(a) after TMD + VOO were less than those in the control group (P = 0.046) in which an increase (P = 0.035) was observed. No changes were observed in urinary albumin or albumin/creatinine ratio.ConclusionsIndividuals at high risk of cardiovascular disease (CVD) who improved their diet toward a TMD pattern reduced their N‐terminal pro‐brain natriuretic peptide compared with those assigned to a low‐fat diet. The same was found for in vivo oxidized low‐density lipoprotein and lipoprotein(a) plasma concentrations after the TMD + VOO diet. From our results TMD could be a useful tool to mitigate against risk factors for heart failure. From our results TMD could modify markers of heart failure towards a more protective mode.