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ObjectiveTo examine the association between consumption of ultra-processed foods and risk of colorectal cancer among men and women from three large prospective cohorts.DesignProspective cohort study with dietary intake assessed every four years using food frequency questionnaires.SettingThree large US cohorts.ParticipantsMen (n= 46 341) from the Health Professionals Follow-up Study (1986-2014) and women (n=159 907) from the Nurses’ Health Study (1986-2014; n=67 425) and the Nurses’ Health Study II (1991-2015; n=92 482) with valid dietary intake measurement and no cancer diagnosis at baseline.Main outcome measureAssociation between ultra-processed food consumption and risk of colorectal cancer, estimated using time varying Cox proportional hazards regression models adjusted for potential confounding factors.Results3216 cases of colorectal cancer (men, n=1294; women, n=1922) were documented during the 24-28 years of follow-up. Compared with those in the lowest fifth of ultra-processed food consumption, men in the highest fifth of consumption had a 29% higher risk of developing colorectal cancer (hazard ratio for highest versus lowest fifth 1.29, 95% confidence interval 1.08 to 1.53; P for trend=0.01), and the positive association was limited to distal colon cancer (72% increased risk; hazard ratio 1.72, 1.24 to 2.37; P for trendConclusionsIn the three large prospective cohorts, high consumption of total ultra-processed foods in men and certain subgroups of ultra-processed foods in men and women was associated with an increased risk of colorectal cancer. Further studies are needed to better understand the potential attributes of ultra-processed foods that contribute to colorectal carcinogenesis.