Background and objectives Achieving accurate real-time optical diagnoses of colorectal polyps with high-confidence predictions is crucial for appropriate decision-making in daily practice. The dual-focus (DF) magnification mode helps endoscopists scrutinize subtle features of polyp surfaces and vessel patterns. This prospective study aimed to evaluate the impact of DF imaging on enhancing the rate of high-confidence narrow-band imaging (NBI)-based optical diagnosis. Methods Consecutive adult patients who underwent colonoscopy and had small colorectal polyps (<10 mm) were enrolled between September 2022 and May 2023. The optical diagnosis of each polyp was evaluated during colonoscopy in two stages by the same endoscopist, utilizing NBI with DF magnification (NDB-DF). A confidence level was assigned to each prediction. High confidence was indicated by clinical judgment when a polyp exhibited distinctive features associated solely with one histological subtype and lacked characteristics of any other subtype. All procedures were carried out with a prototype 190 series Exera III NBI system (Olympus Corporation, Tokyo, Japan) with DFmagnification. Results The study included 413 patients with 623 polyps, comprising 483 ≤ 5 mm and 140 measuring 6-9 mm. The majority were low-grade adenomas (343 lesions), with 17 identified as high-grade adenomas, and none characterized as deep submucosal invasive carcinomas. NBI-DF significantly improved the rate of high-confidence optical diagnoses compared to NBI for both ≤ 5 mm polyps (93.1% vs. 87.5%, p < 0.0001) and 6-9 mm polyps (97.9% vs. 94.2%, p = 0.03). Furthermore, DF significantly facilitated the assessment of microvessel and surface pattern criteria (p < 0.01). Conclusion DF magnification markedly enhanced the rate of high-confidence NBI-based optical predictions for small colorectal polyps. This technique demonstrates the potential for improving the diagnostic yield in real-time optical diagnosis of colorectal polyps in the Vietnamese setting.