Background: High fruit and vegetable intakes may limit weight gain, particularly in susceptible persons, such as those who stop smoking.Objective: The objective was to assess the association of fruit and vegetable intake with subsequent weight change in a large-scale prospective study.Design: The data used were from 89,432 men and women from 5 countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC). The association between fruit and vegetable intake and weight change after a mean follow-up of 6.5 y was assessed by linear regression. Polytomous logistic regression was used to evaluate whether fruit and vegetable intake relates to weight gain, weight loss, or both.Results: Per 100-g intake of fruit and vegetables, weight change was -14 g/y (95% CI: -19, -9 g/y). In those who stopped smoking during follow-up, this value was -37 g/y (95% CI: -58, -15 g/y; P for interaction, 0.0001). When weight gain and loss were analyzed separately per 100-g intake of fruit and vegetables in a combined model, the odds ratios (95% CIs) were 0.97 (0.95, 0.98) for weight gain >= 0.5 and = 1 kg/y, and 0.97 (0.95, 0.99) for weight loss >= 0.5 kg/y. In those who stopped smoking during follow- up, the odds ratios (95% CIs) were 0.93 (0.88, 0.99), 0.87 (0.81, 0.92), and 0.97 (0.88, 1.07), respectively (P for interaction <0.0001).Conclusions: Fruit and vegetable intake relates significantly, albeit weakly inversely, to weight change. For persons who stop smoking, high fruit and vegetable intakes may be recommended to reduce the risk of weight gain. Am J Clin Nutr 2009; 90: 202-9.