BACKGROUND: The effect of the cardioprotective Mediterranean diet on the development of cardiac abnormalities and prognosis of cardiac patients has rarely been investigated. OBJECTIVE: We sought to evaluate the relation between the Mediterranean diet, the development of left ventricular systolic dysfunction (LVSD) at hospitalization, and the 2-y prognosis of patients who have had an acute coronary syndrome (ACS). DESIGN: During 2006-2009, 1000 consecutive patients with ACS were enrolled; of these patients, 459 had LVSD (ejection fraction <40%) at hospitalization [367 men with a mean (+/-SD) age of 64 +/- 14 y, and 92 women aged 71 +/- 12 y], whereas 541 had preserved left ventricular systolic function (421 men aged 62 +/- 12 y, and 120 women aged 67 +/- 12 y). Adherence to the Mediterranean diet was assessed by the validated Mediterranean Diet Score (MedDietScore; theoretical range: 0-55). RESULTS: The MedDietScore was associated with less likelihood of developing LVSD at hospitalization [odds ratio (OR) per 1/55 unit: 0.93; 95% CI: 0.88, 0.99; P = 0.04], less likelihood of remodeling (ie, ejection fraction <50% at 3 mo follow-up; OR: 0.90; 95% CI: 0.78, 1.03: P = 0.06), and less likelihood of recurrent cardiovascular disease events during the 2 y of follow-up (OR: 0.88; 95% CI: 0.80, 0.98; P = 0.04), after adjustment for various confounders. CONCLUSIONS: Greater adherence to the Mediterranean diet seems to preserve left ventricular systolic function and is associated with better long-term prognosis of patients who have had an ACS.