BACKGROUND & AIMS:Given the enormous health, economic and societal consequences of the obesity pandemic, identifying effective primary prevention strategies represents a global priority. The aim of this study was to provide evidence on the association between adherence to a food-based score reflecting a set of targeted, well-informed, simple dietary recommendations and the incidence of overweight/obesity. METHODS:A total of 11,349 initially free of overweight/obesity young adults (mean [SD] age: 34.7 y [10.7]), were followed up biennially during a median of 9.3 years. The Dietary Obesity-Prevention Score (DOS) was created based on a priori evidence of foods associated with weight changes. The DOS positively weighted the consumption of vegetables, fruits, legumes, yogurt, nuts, fish, and a ratio of vegetable to animal protein; whereas the consumption of red meat, processed meat, saturated animal fat, refined grains, ultra-processed food, sugary beverages, beer and spirits were inversely weighted. Energy-adjusted tertiles of each item were used to build the DOS, ranging from 14 (lowest adherence) to 42 points (highest adherence). Adherence to the DOS was calculated at baseline and after 10 years of follow-up. We assessed both incident overweight/obesity (BMI ≥25 kg/m2) and average yearly weight changes in grams per year (g/y). RESULTS:During 104,887 person-years, 2153 incident cases of overweight/obesity were identified. A higher adherence to the DOS at baseline was significantly associated with lower risk of future development of overweight/obesity [multivariable-adjusted HR (95% CI) for the highest vs. lowest quintile = 0.63 (0.54-0.74)], with a significant linear dose-response relationship (p for trend < 0.001). When the analyses were updated with repeated measures, the results were similar and remained statistically significant. Consistently, increases in average yearly weight gain were significantly lower with better adherence to the DOS. CONCLUSIONS:In this Mediterranean cohort of university graduates, a higher adherence to a food-based score was significantly associated with lower risk of overweight/obesity and lower average annual weight gain. These findings may help counsel patients regarding dietary risks and raise awareness of weight gain before the onset of overweight/obesity.