The efficacy of prophylactic hemostasis with endoclips after polypectomy is still controversial. The purpose of this study is to evaluate the efficacy of prophylactic hemostasis for postpolypectomy mucosal defects using endoclips under infrared imaging. Patients with colon polyps who were endoscopically treated at Jikei University Aoto Hospital were retrospectively reviewed to compare the delayed bleeding rate in the infrared imaging group with the conventional imaging group. A total of 813 colon polyps in 416 patients were endoscopically treated from July 2003 to November 2006. The overall postpolypectomy bleeding rate in the infrared imaging group was shown to be significantly lower than in the conventional imaging group. The postpolypectomy bleeding from the endoclip site was also significantly lower in the infrared imaging group than in the conventional imaging group. Even the number of applied endoclips was significantly fewer in the infrared group than the conventional group. The prophylactic use of endoclips with infrared imaging effectively reduced the postpolypectomy bleeding with fewer clip applications.