BACKGROUND: The French dietary guidelines were updated in 2017, and an adherence score to the new guidelines (Programme National Nutrition Santé Guidelines Score 2 [PNNS-GS2]) has been developed and validated recently. Since overweight and obesity are key public health issues and have been related to major chronic conditions, this prospective study aimed to measure the association between PNNS-GS2 and risk of overweight and obesity, and to compare these results with those for the modified Programme National Nutrition Santé Guidelines Score (mPNNS-GS1), reflecting adherence to 2001 guidelines. METHODS AND FINDINGS: Participants (N = 54,089) were recruited among French adults (≥18 years old, mean baseline age = 47.1 [SD 14.1] years, 78.3% women) in the NutriNet-Santé web-based cohort. Mean (SD) score was 1.7 (3.3) for PNNS-GS2 and 8.2 (1.6) for mPNNS-GS1. Selected participants were those included between 2009 and 2014 and followed up to September 2018 (median follow-up = 6 years). Collected data included at least three 24-hour dietary records over a 2-year period following inclusion, baseline sociodemographics, and anthropometric data over time. In Cox regression models, PNNS-GS2 was strongly and linearly associated with a lower risk of overweight and obesity (HR for quintile 5 versus quintile 1 [95% CI] = 0.48 [0.43-0.54], p < 0.001, and 0.47 [0.40-0.55], p < 0.001, for overweight and obesity, respectively). These results were much weaker for mPNNS-GS1 (HR for quintile 5 versus quintile 1 = 0.90 [0.80-0.99], p = 0.03, and 0.98 [0.84-1.15], p = 0.8, for overweight and obesity, respectively). In multilevel models, PNNS-GS2 was negatively associated with baseline BMI and BMI increase over time (β for a 1-SD increase in score [95% CI] = -0.040 [-0.041; -0.038], p < 0.001, and -0.00080 [-0.00094; -0.00066], p < 0.001, respectively). In "direct comparison" models, PNNS-GS2 was associated with a lower risk of overweight and obesity, lower baseline BMI, and lower BMI increase over time than mPNNS-GS1. Study limitations include possible selection bias, reliance on participant self-report, use of arbitrary cutoffs in data analyses, and residual confounding, but robustness was tested in sensitivity analyses. CONCLUSIONS: Our findings suggest that adherence to the 2017 French dietary guidelines is associated with a lower risk of overweight and obesity. The magnitude of the association and the results of the direct comparison reinforced the validity of the updated recommendations.