Background: There is a worldwide shift towards increased consumption of ultra-processed foods (UPF) with concurrent rising prevalence of obesity. We examined the relationship between the consumption of UPF and weight gain and risk of obesity. Methods: This prospective cohort included 348 748 men and women aged 25-70 years. Participants were recruited between 1992 and 2000 from 9 European countries in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Two body weight measures were available, at baseline and after a median follow-up time of 5 years. Foods and drinks were assessed at baseline by dietary questionnaires and classified according to their degree of processing using NOVA classification. Multilevel mixed linear regression was used to estimate the association between UPF consumption and body weight change (kg/5 years). To estimate the relative risk of becoming overweight or obese after 5 years we used Poisson regression stratified according to baseline body mass index (BMI). Results: After multivariable adjustment, higher UPF consumption (per 1 SD increment) was positively associated with weight gain (0.12 kg/5 years, 95% CI 0.09 to 0.15). Comparing highest vs. lowest quintile of UPF consumption was associated with a 15% greater risk (95% CI 1.11, 1.19) of becoming overweight or obese in normal weight participants, and with a 16% greater risk (95% CI 1.09, 1.23) of becoming obese in participants who were overweight at baseline. Conclusions: These results are supportive of public health campaigns to substitute UPF for less processed alternatives for obesity prevention and weight management. (c) 2021 Published by Elsevier Ltd.