BACKGROUND/AIMS: The real-world efficacy of computer-aided detection (CADe) systems, such as GI Genius (Medtronic), is unclear. We examined the colonoscopy metrics using CADe alone and with a mucosal exposure device (EndoCuff; Olympus) in a real-world setting. METHODS: We retrospectively reviewed screening and surveillance colonoscopies before, during, and after CADe use in a large tertiary care center. Outcomes included the adenomas per colonoscopy (APC), sessile serrated lesions per colonoscopy, adenoma detection rate (ADR), sessile serrated lesion detection rate (SSLDR), advanced ADR, total polyp detection rate, and true histology rate. The ADR and SSLDR were further examined according to size, colon location, and EndoCuff use. RESULTS: A total of 798 colonoscopies were performed, including 386 pre-CADe, 178 CADe, and 234 post-CADe. In cases where CADe was used with the EndoCuff, the 1 to 5 mm ADR increased from 36.3% (pre-CADe) to 52.1% (CADe) (p=0.01). The 1 to 5 mm SSLDR increased from 9.6% (pre-CADe) to 17.1% (CADe) (p=0.02). The right-sided ADR increased from 30.8% (pre-CADe) to 42.7% (CADe) (p=0.03). The right-sided SSLDR increased from 12.3% (pre-CADe) to 24.8% (CADe) (p<0.001). No significant changes were observed when only CADe was used. No differences were found in other outcome measures. Post-CADe metrics returned to pre-CADe levels. CONCLUSIONS: GI Genius is useful for identifying small and right-sided polyps only when used with the EndoCuff.