Endoscopic resection of luminal gastrointestinal neoplasia offers a minimally invasive, lower risk alternative that can be successful in the appropriate setting. Bleeding and perforation can occur with endoscopic mucosal resection and endoscopic submucosal dissection. Defect closure with conventional endoclips or modified technique using endoloops can decrease the risk of adverse events. The Overstitch (Apollo Endosurgery, Austin, TX) endoscopic suturing device is designed for tissue apposition and thus can effectively close a large resection defect. Herein we describe our technique. Our and other groups’ initial experience with suturing for closure of the resection defect demonstrates high procedural success rates and safety.