BACKGROUND AND AIMS: Recently, the use of computer-aided detection (CADe) for colonoscopy has been investigated to improve the adenoma detection rate (ADR). We aimed to assess the efficacy of a regulatory-approved CADe in a large-scale study with high numbers of patients and endoscopists. METHODS: This was a propensity score matched prospective study that took place at a university hospital between July 2020 and December 2020. We recruited patients aged ≥20 years who were scheduled for colonoscopy. Patients with polyposis, inflammatory bowel disease, or incomplete colonoscopy were excluded. We used a regulatory-approved CADe and conducted a propensity score matching-based comparison of the ADR between patients examined with and without CADe as the primary outcome. RESULTS: During the study period, 2,261 patients underwent colonoscopy with the CADe system or routine colonoscopy and 175 patients were excluded in accordance with the exclusion criteria. Thirty endoscopists (9 nonexperts and 21 experts) were involved in this study. Propensity score matching was conducted using 5 factors, resulting in 1,836 patients included in the analysis (918 patients in each group). The ADR was significantly higher in the CADe group than in the control group (26.4% vs 19.9%, respectively; relative risk [OR], 1.32; 95% confidence interval [CI], 1.12-1.57); however, there was no significant increase in the advanced neoplasia detection rate (3.7% vs 2.9%, respectively). CONCLUSIONS: The use of the CADe system for colonoscopy significantly increased the ADR in a large-scale prospective study including 30 endoscopists. (UMIN-CTR: UMIN000040677.).