We developed a suturing method with string and clips for a single-channel endoscope. The feasibility of the string clip suturing method is evaluated in this prospective pilot study. This study involved 10 consecutive patients who underwent endoscopic submucosal dissection (ESD) for a duodenal tumor. Polyester string was tied to the arm of a partially out thrust clip. The clip and string can be passed through the instrument channel (3.2mm) of a single-channel endoscope. The clip with string was placed at the distal edge of the large mucosal defect. A second clip was hooked on the string and placed on the opposite side. Both clips were gathered by pulling the free end of the string, and additional clips were placed to achieve complete closure. This method was compared with that for the previous 10 patients without mucosal closure after duodenal ESD. Mean size of resected specimens was 39.1 ± 12.4mm. The success rate of the string clip suturing method was 100% (10/10). The mean procedure time was 23.4 ± 13.8 minutes. Perforation during ESD occurred in 1 patient and was successfully closed by this method. None of the treated patients developed serious adverse events after the procedure. Compared with the no-suture group, the length of stay was significantly shorter (P=.038). The string clip suturing method appears to be a safe and effective method for closure of large mucosal defects. (Clinical trial registration number: UMIN000023698.).