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Background: Differentiating sessile serrated adenoma/polyp (SSA/P) from hyperplastic polyp (HP) is clinically important in determining the necessity of endoscopic resection or recommending appropriate surveillance. There are few reports of characterization of SSA/P using narrowband imaging and chromoendoscopy with and without magnification. We aimed to establish imaging criteria to aid real-time diagnosis of SSA/P., Methods: Patients with pale sessile or flat lesions of 6 mm or greater were prospectively enrolled in this multicenter trial. Nine endoscopic criteria, determined in real time, were investigated for possible association with SSA/P. Endoscopic mucosal resection was performed; specimens were retrieved and analyzed by histopathological examination., Results: In 63 patients, 89 lesions were detected, including 41 HP, 38 SSA/P, five mixed polyps, and five other lesions. Right-side colon location, lesion size of 10 mm or greater, excessive mucus, the presence of a varicose microvascular vessel (VMV) noted with high-magnification narrowband imaging, and type III(H) pit pattern were each commonly associated with SSA/P compared with HP. Multivariate analysis substantiated three independent endoscopic criteria for SSA/P: the presence of VMV (p = 0.001), lesion size of 10 mm or greater (p = 0.0017), and right-side location (p = 0.0041), with odds ratios of 8.2, 7.2, and 6.1, respectively. The presence of VMV had a significantly higher specificity (87.8%) than the other two independent endoscopic criteria (p = 0.0007 and p = 0.0008, respectively), but a lower sensitivity (57.9%), whereas a combination of the three criteria (two or more positive) increased the sensitivity significantly (89.5% and p = 0.0033) and had a higher degree of accuracy (82.3%)., Conclusions: Three endoscopic criteria individually and in combination were effective in predicting a diagnosis of SSA/P without the need for chromoendoscopy.