The present study was performed to evaluate the therapeutic safety and feasibility of purse-string sutures with nylon loops and metal clips under single-channel endoscopy to repair gastrointestinal wall defects that had previously developed during endoscopic full-thickness resection (EFR). A multicenter prospective cohort study of 42 patients who had developed defects of the gastrointestinal wall during EFR was conducted from April 2012 to October 2016. All lesions were endoscopically repaired with either a single-channel gastroscope (research group, n=18) or double-channel gastroscope (control group, n=24). The patients' clinical features, purse-string suturing times and complication rates were analyzed. There was no significant difference in the perforation rate between the research and control groups. There were also no significant differences in the purse-string suturing time (research vs. control group, 10.5 vs. 14.6 min, respectively; P=0.214), specimen size or complication rate (subcutaneous emphysema) between the two groups. No recurrences were observed during the follow-up period. The current data suggest that application of purse-string sutures with nylon loops and metal clips for repair of EFR-induced gastrointestinal wall defects may be safely and feasibly applied under single-channel gastroscopy as well as under double-channel gastroscopy.