Classically, foods have been classified based on their botanical or animal origin and/or their nutritional composition. However, as a result of the nutrition transition and the increasing consumption and availability of highly processed foods in the last decade, ultra-processed foods (UPF) have been defined with different classification systems – NOVA being one of the most well-known. A new analysis from the PREDIMED study evaluated potential differences in the association between UPF consumption and cardiometabolic markers, as well as the nutritional profile of subjects with higher or lower UPF consumption, using four food processing-based classification systems on the same dataset. Results revealed that individuals with the highest UPF consumption had a higher intake of energy, sugars, saturated fat and sodium, as well as lower fiber intake, lower adherence to the Mediterranean Diet and a higher glycemic load than those with the lowest UPF consumption, regardless of the classification method. Nevertheless, applying different food processing-based classification systems resulted in different associations between UPF consumption and cardiometabolic markers. For example, only when the NOVA classification was used did the group with the highest UPF consumption show significantly higher BMI than the lowest consumption group. These results support the importance of standardizing criteria to classify processed foods, as this will ultimately allow epidemiological research to be effectively translated into guidelines for the general public. In any case, there is no doubt that minimally processed foods and culinary ingredients like extra virgin olive oil still represent the foundation of a healthy diet.