BACKGROUND AND AIMS: The nutrient profile underlying the Nutri-Score, a front-of-pack nutrition label, was updated in 2022-2023 by an ad-hoc scientific committee. Validation studies regarding the predictive ability of nutrient profile are a key step in supporting evidence-based policies. This prospective study aimed to investigate the associations between the 2023 Nutri-Score nutrient profile model (2023 NS-NPM) with weight change, risk of overweight and obesity, and to compare it with the 2015 Nutri-Score nutrient profile (2015 NS-NPM). METHODS: Participants from the NutriNet-Santé cohort were recruited among French adults (N = 75 775). An individual dietary index was computed to characterize the nutritional quality of diets based on at least three 24 h-dietary records, as the average nutritional score of each food consumed weighted by their caloric contribution. Proportional Cox hazard models were used to assess the association with the indices, obesity and overweight onset and mixed models for weight gain over time. RESULTS: We found that a higher 2023 NS-NPM dietary index (DI) (i.e. a less healthy diet) was associated with a significant higher increase in BMI over time (+ 0.24% [0.22-0.26] BMI/ year in Tertile 3 vs. Tertile 1) and an increased risk of overweight (HR(T3 vs. T1)=1,33 [1.24 - 1.43]) or obesity onset (HR(T3 vs. T1)=1.29 [1.14-1.45]). The comparison between the 2023 NS-NPM DI and the 2015 NS-NPM DI did not detect a statistically significant difference in terms of predictive ability. CONCLUSION: These results contribute to the validation of the 2023 Nutri-Score nutrient profile, supporting its use as public health tool for chronic disease prevention.