The international scientific community has long agreed on the fact that a low-fat diet is actually able to bring benefits to cardiovascular health and beyond. By low-fat diet, experts mean a diet where the average calories assimilated daily are made up of no more than 30% fat. The Mediterranean Diet, on the other hand, identifies a nutritional model inspired by the traditional eating habits of the countries bordering the Mediterranean Sea. It began to be studied scientifically in the 1950s and it is still today one of the diets that have a positive impact on our health when associated with correct lifestyles. Although epidemiological and mechanistic studies show similar results, there is no evidence from large-scale, long-term clinical trials on the efficacy of the Mediterranean Diet compared with another active group, particularly in secondary prevention. A convincing response has been obtained from the recent CORDIOPREV study (CORonary Diet Intervention with Olive oil and cardiovascular PREVention) which randomized ∼1000 patients with documented coronary artery disease to a Mediterranean Diet or a low-fat dietary intervention. In a 7-year follow-up, the Mediterranean Diet was superior to the low-fat diet in the prevention of major cardiovascular events.