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Nutrition in secondary prevention of Acute Coronary Syndrome (ACS) is inadequately investigated. We sought to evaluate the role of Mediterranean diet in prognosis of first-diagnosed ACS patients, according to heart failure type.In 2006-2009, 1000 consecutive patients hospitalized at First Cardiology Clinic of Athens with ACS diagnosis were enrolled in the study. In 2016, 10-year follow-up was performed (75% participation rate). Only n = 690 (69%) first-diagnosed ACS patients were included. Adherence to Mediterranean diet was assessed through MedDietScore (range 0-55). Heart failure phenotypes were reduced, mid-range and preserved ejection fraction (that is, HFrEF, HFmrEF and HFpEF, respectively).Ranking from first to third MedDietScore tertile, fewer 1, 2 and 10-year fatal/non-fatal ACS events were observed. Multivariate logistic regression analysis highlighted a significantly inverse association between MedDietScore and long-term ACS prognosis in 1 year (odds ratio (OR) = 0.84, 95% confidence interval (CI) (0.71, 1.00), P = 0.05), 2 year (OR = 0.91, 95% CI (0.82, 1.00), P = 0.04) and 10 year (OR = 0.93, 95% CI (0.85, 1.00), P = 0.05) follow-up. Further analysis revealed that MedDietScore differentially affected patients' prognosis according to heart failure phenotype, with short-term impact in HFrEF and HFmrEF patients yet longer positive outcomes in HFpEF and C-reactive protein potentially mediated these relations.Mediterranean diet seemed to protect against recurrent cardiac episodes in coronary patients with major ACS complications. Results were more encouraging with regard to patients with preserved left ventricle function. Such findings may possess a cost-effective, supplementary-to-medical, treatment approach in this patient category where evidence concerning their management are inconclusive.