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The aim of the present study was to evaluate the safety of prophylactic endoclipping before resection of large pedunculated colorectal polyps in patients with uninterrupted anticoagulation or antiplatelet therapy.In a single tertiary referral center, patients with normal coagulation parameters and those with uninterrupted anticoagulation or antiplatelet medications, who underwent prophylactic endoclipping before resection of large pedunculated colorectal polyps (polyp’s head diameter >10 mm), were evaluated retrospectively. Demographic, clinical, and laboratory parameters, polyp characteristics, number of clips used for endoclipping, histology of resected polyps, the polypectomy technique, and postpolypectomy complications were recorded and compared.In 64 patients with large pedunculated colorectal polyps, successful endoclipping before resection was achieved. Eleven patients (17.2%) had uninterrupted anticoagulation (n=4) or antiplatelet (n=7) medications. Statistical analysis showed no significant differences in age, sex, indications for colonoscopy, location of polyps, size of polyp head or stalk, coexisting small polyps, histology of resected polyps, and polypectomy techniques among patients with normal coagulation parameters (group A) and patients on uninterrupted anticoagulant or antiplatelet treatment (group B). Coronary artery disease, hypertension, and atrial fibrillation were significantly more prevalent in group B. No immediate or delayed postpolypectomy hemorrhage occurred in either group. One patient (1.9%) in group A developed postpolypectomy coagulation syndrome and was successfully treated conservatively. Follow-up evaluation demonstrated no recurrence of polyps or cancer development.According to our experience, uncomplicated polypectomy of large pedunculated colorectal polyps can be performed by prophylactic endoclipping in patients receiving anticoagulation or antiplatelet medications.