Background: Fruit and vegetable consumption might prevent weight gain through their low energy density and high dietary fiber content. Objective: We assessed the association between the baseline consumption of fruit and vegetables and weight change in participants from 10 European countries participating in the European Prospective Investigation into Cancer and Nutrition study. Design: Diet was assessed at baseline in 373,803 participants by using country-specific validated questionnaires. Weight was measured at baseline and self-reported at follow-up in most centers. Associations between baseline fruit and vegetable intakes (per 100 g/d) and weight change (g/y) after a mean follow-up of 5 y were assessed by using linear mixed-models, with age, sex, total energy intake, and other potential confounders controlled for. Results: After exclusion of subjects with chronic diseases at baseline and subjects who were likely to misreport energy intakes, baseline fruit and vegetable intakes were not associated with weight change overall. However, baseline fruit and vegetable intakes were inversely associated with weight change in men and women who quit smoking during follow-up. We observed weak positive associations between vegetable intake and weight change in women who were overweight, were former smokers, or had high prudent dietary pattern scores and weak inverse associations between fruit intake and weight change in women who were >50 y of age, were of normal weight, were never smokers, or had low prudent dietary pattern scores. Conclusions: In this large study, higher baseline fruit and vegetable intakes, while maintaining total energy intakes constant, did not substantially influence midterm weight change overall but could help to reduce risk of weight gain in persons who stop smoking. The interactions observed in women deserve additional attention.