Endoscopic submucosal dissection (ESD) and resection of stomach and colon tumors have become common. However, mucosal defects resulting from ESD may cause delayed bleeding and perforation. To prevent adverse events, we developed a new clip closure technique, namely, the loop and open-close clip closure method (LOCCM), and aimed to examine its efficacy after ESD for stomach and colon tumors. The LOCCM uses loop and open-close clips. Here, the open-close clip was used to grasp the loop to bring it to the edge of the post-ESD mucosal defect. Another clip with a loop was then inserted into the opposite edge and clipped to the contralateral mucosa to pull both edges together. Once apposed, additional clips facilitated complete closure. The LOCCM was performed in 19 patients after ESD at Tottori University between October 2020 and March 2021. The outcomes retrospectively analyzed were the LOCCM success and adverse event rates. The complete closure rate using LOCCM was 89.5% and none of the patients had post-ESD bleeding or perforation. The results show that LOCCM is an effective and safe closure technique for mucosal defects after stomach and colon ESD to prevent bleeding and perforation.