ABSTRACT: BACKGROUND:Food preparation behaviors may markedly determine dietary intake and consequently influence weight status. However, the few available studies have found equivocal results. No study has prospectively investigated the association between food preparation behaviors and weight change over time. We estimated the associations of food preparation behaviors with the 5-year relative weight change and the risk of developing obesity in 12,851 French adults participating in the NutriNet-Santé cohort study. The mediating effect of dietary intake was also addressed. METHODS:Frequency and time for meal preparation, cooking skills, preparation from scratch, kitchen equipment, cooking enjoyment, willingness to cook better/more frequently and dietary intake were assessed at baseline using web-based questionnaire and 24 h records, respectively. Self-reported anthropometric data were collected using questionnaire, at baseline and after 5 years of follow-up. Associations of such behaviors with 5-year relative weight change and the mediation analyses were assessed through multivariate linear regression models, and obesity risk was analyzed with logistic regression, stratified by sex and adjusted for age, household composition, education, occupation, income, physical activity, smoking and history of dieting. RESULTS:In women, preparation from scratch was prospectively associated with a decreased risk of obesity over the 5-year follow-up (OR?=?1.32 (1.08; 2.32)) after adjustment. After including dietary mediating factors, the association between preparation from scratch and obesity risk in women did not remain significant (P?=?0.08). This association appeared to be partly mediated by dietary factors with a difference of 59% of the estimate, in the group with the low score, between the adjusted model and those with mediators (OR?=?1.13 (0.71; 1.77)). Regarding 5-year relative weight change, after adjustment for confounding factors, all associations between indicators of food preparation behaviors and weight change became non significant. CONCLUSIONS:In the context from reduced time spent preparing meals that could have an impact on dietary quality and health in industrialized countries, our prospective study does not show effect of food preparation behaviors on 5-year relative weight change and obesity risk, except for preparation from scratch on obesity risk in women. Our study provides useful information about the long term implications of food preparation behaviors on health and should be corroborated by future studies, particularly on the effect of food preparation behaviors on chronic diseases such as incident diabetes, hypertension or cardiovascular diseases, compared with other determinants. TRIAL REGISTRATION:NCT03335644 on ClinicalTrials.gov.