Endoscopic polypectomy is the first-line treatment for colorectal polyps. However, this procedure carries an increased risk of bleeding in patients with hemostatic disorders, particularly in the presence of a large pedunculated polyp. We report the case of a 52-year-old man with hemophilia A and associated von Willebrand factor deficiency, admitted for rectal bleeding evolving over the previous year. Laboratory investigations revealed severe iron-deficiency anemia and a reduced factor VIII level. Colonoscopy showed a large pedunculated sigmoid polyp located 50 cm from the anal verge, with a 15 mm stalk and a 30 mm head. A multidisciplinary approach involving gastroenterologists and hematologists allowed endoscopic polypectomy to be performed using a hot snare after hemostatic preparation with coagulation factor concentrates and tranexamic acid, together with prophylactic placement of an end loop. No periprocedural or postprocedural bleeding complications were observed. Histopathological examination revealed a tubulovillous adenoma with low-grade dysplasia, with complete resection and negative margins. This case highlights that endoscopic polypectomy can be safely performed in a hemophilic patient, provided that careful preparation, appropriate hemostatic prophylaxis, and preventive endoscopic techniques are used.