Key PointsQuestionIs body mass index (BMI) or changing BMI associated with risk of gastrointestinal cancer?FindingsThis cohort study, which used data from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, found that overweight and obese BMI in early and middle adulthood was associated with an increased risk of gastrointestinal cancer. Maintaining or increasing overweight or obese BMI over time was also associated with an increased risk of gastrointestinal cancer.MeaningThese findings suggest that overweight and obese BMI over time may increase one’s risk of gastrointestinal cancer.