Colon polyp detection and removal via colonoscopy are essential for colorectal cancer screening and prevention. This study aimed to develop a colon polyp detection program based on the RetinaNet algorithm and verify its clinical utility. To develop the AI-assisted program, the dataset was fully anonymized and divided into 10 folds for 10-fold cross-validation. Each fold consisted of 9,639 training images and 1,070 validation images. Video data from 56 patients were used for model training, and transfer learning was performed using the developed still image-based model. The final model was developed as a real-time polyp-detection program for endoscopy. To evaluate the model’s performance, a prospective randomized controlled trial was conducted at six institutions to compare the polyp detection rates (PDR). A total of 805 patients were included. The group that utilized the AI model showed significantly higher PDR and adenoma detection rate (ADR) than the group that underwent colonoscopy without AI assistance. Multivariate analysis revealed an OR of 1.50 for cases where polyps were detected. The AI-assisted polyp-detection program is clinically beneficial for detecting polyps during colonoscopy. By utilizing this AI-assisted program, clinicians can improve adenoma detection rates, ultimately leading to enhanced cancer prevention.