• Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
• Department of Nutrition and Food Hygiene, School of Public Health and Management, Chongqing Medical University, Chongqing, China.
• Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Whether ultra-processed food consumption is associated with the risk of pancreatic cancer has not been determined. We performed a prospective study to fill this gap. A population-based cohort of 98265 American adults was identified from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Ultra-processed foods were defined by the NOVA classification. Cox regression was used to estimate hazard ratios (HRs) for pancreatic cancer incidence. Subgroup analysis was performed to identify the potential effect modifiers. During a mean follow-up of 8.86 years, 387 pancreatic cancer cases occurred. High consumption of ultra-processed foods was found to be associated with an increased risk of pancreatic cancer [fully adjusted HR_{quartile4 vs. 1} : 1.49; 95% confidence interval (CI): 1.07, 2.07; P_trend =0.021] in a linear dose-response manner (P_nonlinearity =0.075). Subgroup analysis further found that the positive association of ultra-processed food consumption with the risk of pancreatic cancer was more pronounced in subjects aged <65 years (HR_{quartile4 vs. 1} : 2.17; 95% CI: 1.14, 4.15) than in those with aged ≥65 years (HR_{quartile4 vs. 1} : 1.32; 95% CI: 0.88, 1.94), though the interaction test failed to achieve the statistical significance (P_interaction =0.061). These findings suggest that reducing ultra-processed food consumption may be beneficial in decreasing pancreatic cancer incidence. This article is protected by copyright. All rights reserved.