Nutrient profiling systems (NPS) are used to classify foods according to their nutritional composition. However, investigating their prospective associations with health is key to their validation. The study investigated the associations of the original Food Standards Agency (FSA)-NPS and three variants (Food Standards Australia New Zealand Nutrient Profiling Scoring Criterion (NPSC), Health Star Rating NPS and the French High Council of Public Health NPS (HCSP-NPS)), with weight status. Individual dietary indices based on each NPS at the food level were computed to characterise the dietary quality of 71 403 French individuals from the NutriNet-Santé cohort. Associations of these indices with weight gain were assessed using mixed models and with overweight and obesity risks using Cox models. Participants with a higher dietary index (reflecting lower diet nutritional quality) were more likely to have a significant increase in BMI over time (β-coefficients positive) and an increased risk of overweight (hazard ratio (HR) T3 v. T1 = 1·27 (95 % CI 1·17, 1·37)) for the HCSP-Dietary Index, followed by the original FSA-Dietary Index (HR T3 v. T1 = 1·18 (95 % CI 1·09, 1·28)), the NPSC-Dietary Index (HR T3 v. T1 = 1·14 (95 % CI 1·06, 1·24)) and the Health Star Rating-Dietary Index (HR T3 v. T1 = 1·12 (95 % CI 1·04, 1·21)). Whilst differences were small, the HCSP-Dietary Index appeared to show significantly greater association with overweight risk. Overall, these results show the validity of NPS derived from the FSA-NPS, supporting their use in public policies for chronic disease prevention.