Recently, a through-the-scope suturing (TTSS) system has received FDA approval and has been evaluated for closing mucosal defects postintervention. We hereby performed a systematic review and pooled meta-analysis of available studies to assess the safety and efficacy of this intervention. We queried the following databases through April 26, 2023: Embase, MEDLINE, Cochrane Central Register of Controlled Trials, and Web of Science Core Collection. Endoscopists utilizing TTSS for the following reasons were included: endoscopic mucosal resection, endoscopic submucosal dissection, peroral endoscopic myotomy, perforation, fistula closure, and/or stent fixation. The outcomes assessed were technical success, primary clinical success (closure of defect without additional intervention), and overall clinical success (closure of defect with/without additional intervention). Random effects model with the DerSimonian Laird approach was used to report event rates expressed as proportions with a 95% CI. A total of 12 studies with 512 patients (mean age of 61.5 ± 18.4y, 54.6% females) were included. The technical success rate was 96.0% (CI: 94.3%-97.7%). The primary clinical success rate was 74.8% (CI: 65.5%-84.1%). The overall clinical success rate was 95.4% (CI: 92.6-98.2%). Only 1 mortality case unrelated to intervention was reported. The TTSS appears safe and effective for closing mucosal defects after therapeutic endoscopic interventions. Further cost-effective studies should be performed comparing with endoclips for use in clinical settings.