Background Recent advances in endoscopic tools and techniques have allowed the minimally invasive management of iatrogenic gastrointestinal (GI) perforations and bleedings. However, surgery may be required in cases with larger defects and bleeding refractory to conventional endoscopic modalities. The use of over-the-scope clips (OTSC) has been shown to improve the outcomes in these patients compared with conventional treatment modalities. In this study, we evaluated the safety and efficacy of OTSC for different indications in the GI tract. Methods The data of consecutive patients in whom OTSC was utilized for different indications between February 2017 and October 2019 were analyzed retrospectively. The following outcomes were recorded: technical and clinical success, and adverse events related to the procedure. Results Thirty-six patients (22 male, mean age 52.673±14.97 years, range 11-72 years) underwent OTSC application. Indications for OTSC were: GI defects (perforation n=13, fistula n=5); esophageal metallic stent fixing n=9; GI bleeding n=8; and neuroendocrine tumor endotherapy n=1. The average size of the defect was 15.88±8.01 mm. The technical and clinical success rates were 88.89% and 83.33%, respectively. There were 4 (11.1%) technical failures: colonic perforations n=2; duodenal ulcer bleeding n=1; and esophageal metal stent fixation n=1. There were 2 (9.5%) adverse events, including 1 partial duodenal obstruction and 1 delayed bleeding. Conclusions The use of OTSC is safe, easy and effective for various indications in the GI tract. Prospective trials are required to see if the use of OTSC is cost effective as a primary endoscopic treatment method in these cases.