Nonvariceal upper gastrointestinal bleeding (NVUGIB) is a common and potentially life-threatening condition. Over-the-scope clips (OTSCs) have emerged as a promising endoscopic treatment option for NVUGIB. We aimed to analyze the efficacy and safety of OTSCs compared to standard endoscopic treatments (ST) in patients with NVUGIB. We conducted a comprehensive search of PubMed, Embase, Scopus, and Cochrane Library databases from inception to June 2024 for randomized controlled trials (RCTs) comparing OTSCs with ST for NVUGIB. The primary outcomes were initial hemostasis and persistent bleeding. Secondary outcomes included rebleeding rates, mortality, hospital stays and others. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using random/fixed-effects models. Six RCTs involving 621 patients were included in the meta-analysis. OTSCs demonstrated significantly higher initial hemostasis (OR 4.80, 95% CI 1.78-12.96; P = 0.002) and lower persistent bleeding rates (OR 0.17, 95% CI 0.05-0.56; P = 0.003) compared to ST group. The rebleeding rate was significantly lower in the OTSC group 7-days re-bleeding (OR 0.27, 95% CI 0.14-0.53; P = 0.001); 30-days rebleeding (OR 0.40, 95%CI 0.22, 0.70; P = 0.002). No significant differences were observed in mortality (OR 0.65, 95% CI 0.31-1.33; P = 0.38) and hospital stay (mean difference 0.79days 95%CI -0.57, 2.15) between the two groups. OTSCs are more effective than ST for achieving hemostasis and preventing rebleeding in patients with NVUGIB, without increasing mortality. Key message What is Already Known Previous studies have shown that nonvariceal upper gastrointestinal bleeding (NVUGIB) is a serious medical condition that needs effective endoscopic interventions. The success rates of standard treatments for achieving hemostasis and preventing rebleeding are not consistent. What This Study Adds According to this study, over-the-scope clips (OTSCs) have the same mortality rate as standard endoscopic treatments, but they significantly improve initial hemostasis and lower rebleeding rates. Impact on Research, Practice, or Policy The findings support the use of OTSCs as a preferred intervention for NVUGIB, which could affect clinical guidelines and encourage additional research focused on improving endoscopic techniques and patient outcomes in the management of gastrointestinal bleeding.