BACKGROUND & AIMS: The ability to determine colorectal polyp pathology by endoscopy could reduce the risks of polypectomy and the cost of pathologic evaluation. This study evaluated the ability of the Olympus Exera 180 high-definition colonoscope (Olympus America, Inc, Center Valley, PA), with narrow-band imaging, to predict colorectal polyp histology. METHODS: A library of 320 endoscopic photographs with correlated histologic information was used to identify endoscopic features associated with adenomatous and hyperplastic histology. These features were tested in a prospective study of 451 consecutively identified colorectal polyps. Polyps were observed endoscopically and assigned a designation of high or low confidence. The primary end points were the predictive value of high-confidence endoscopic interpretations of adenoma and hyperplastic histology for polyps 5 mm and smaller in size. RESULTS: Endoscopic predictions of adenoma and hyperplastic histology were made with high confidence for 80% and 83% of cases, respectively. High-confidence predictions were more likely than low-confidence predictions to be correct (P<.001). High-confidence predictions of adenoma and hyperplastic histology were correct for 91% and 95%, respectively, of polyps 5 mm and smaller in size. CONCLUSIONS: Introduction of confidence levels to the endoscopic interpretation of colorectal polyp histology allows sufficient accuracy for the use of the Exera narrow-band imaging system in the identification of distal hyperplastic polyps that do not need resection, as well as to plan postpolypectomy surveillance without pathologic evaluation of polyps 5 mm in size or smaller.