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There are several reports on the use of the over-the-scope clip (OTSC) for gastrointestinal bleeding/fistula and endoscopic iatrogenic perforation. However, there are almost no reports on OTSC use for anastomotic leakage (AL) after colorectal cancer surgery. The purpose of this study was to evaluate the outcome of AL closure using the OTSC. Five patients who had undergone AL after laparoscopic surgery for colorectal cancer from April 2017 to April 2019 were evaluated. The average distance from the anal verge of the anastomosis site was 12 (5–18) cm. The average diameter of the dehiscent part was 10.9 (9.3–14.4) mm. The average number of OTSC days after the occurrence of AL was 11 (5–22). On the contrast examination immediately after OTSC, all cases were completely closed, but in the later contrast examination, only one case remained completely closed. The average incompletely closed diameter was 3.6 (2.9–5.1) mm, and the diameter of the dehiscent part was reduced in all cases. Only one patient ultimately underwent colostomy; the rest were cured with OTSC alone. AL site closure using the OTSC after colorectal cancer surgery is a useful minimally invasive treatment when combined with appropriate drain management. [ABSTRACT FROM AUTHOR]