Multiple randomized controlled trials (RCTs) using the second-generation distal attachment cuff device (Endocuff Vision; Olympus America, Center Valley, Pa, USA) have reported conflicting results in improving adenoma detection rate (ADR) compared with standard high-definition colonoscopy without the distal attachment. We conducted a systematic review and meta-analysis of RCTs to compare outcomes between second-generation cuff colonoscopy (CC) versus colonoscopy without the distal attachment (standard colonoscopy SC). An electronic literature search was performed using PubMed, Google Scholar, Embase, and Cochrane Library through May 2020. The primary outcome was reporting of ADR, and secondary outcomes were polyp detection rate (PDR), mean withdrawal time, mean adenomas per colonoscopy (APC), sessile serrated lesion detection rate, and adverse events. Pooled rates and risk ratios (RRs) with 95% confidence intervals were reported. Eight RCTs with 5695 patients were included in the final analysis, with 2862 patients (mean age, 62.8 years; 52.9% men) in the CC group and 2833 patients (mean age, 62.6 years; 54.2% men) in the SC group. Compared with SC, use of CC was associated with a significant improvement in ADR (49.8% vs 45.6%, respectively; RR, 1.12; P = .02), PDR (58.1% vs 53%, respectively; RR, 1.12; P = .009), and APC (P < .01). Furthermore, use of CC had a .93-minute lower mean withdrawal time (P < .01) when compared with SC. The difference in ADR was larger in the screening/surveillance population (6.5%, P = .02) and when used by endoscopists with ADRs <30% (9.4%, P = .03). The results of this meta-analysis of randomized trials show a significant improvement in ADR and APC with shorter withdrawal times using the second-generation cuff device compared with SC.