Since its market launch in 2007, the endoscopic OTSC clipping system has been the object of intensive clinical research. These data were systematically collected for post-market clinical follow-up (PMCF). The aim of the study was the systematic review of the efficacy and safety of the OTSC System. The PMCF database was systematically searched for clinical data on OTSC therapy of GI hemorrhage (H), acute leaks/perforations (AL) and chronic leaks/fistulae (CL). Major outcomes were successful clip application and durable hemostasis/closure of defects. Comprehensive pooled success proportions were established by meta-analytical methods. Four-hundred-fifty-seven publications were reviewed. Fifty-eight articles comprising 1868 patients fulfilled criteria to be included in the analysis. These consisted of retrospective analyses, prospective observational trials, one randomized-controlled trial (STING) and one quasi-controlled study (FLETRock). The pooled proportion analysis revealed high overall proportions of technical success: H - mean 93.0% 95%CI 90.2-95.4, AL-mean 89.7% 95%CI 85.9-92.9 and CL-mean 83.8% 95%CI 76.9-89.7. Pooled durable clinical success proportions were: H-mean 87.5% 95%CI 80.5-93.2, AL-mean 81.4% 95%CI 77.0-85.3 and CL-mean 63.0% 95%CI 53.0-72.3. By pooling all clinical data gained, we conclude that OTSC application in GI hemorrhage and closure of GI lesions is safe and effective in real clinical use.