<b><i>Background/Aims:</i></b> Post-polypectomy bleeding (PPB) is a major complication of colorectal polypectomy, and antithrombotics is one of the major risk factors of PPB. The purpose of this study was to investigate PPB risks with regard to the combinations of antithrombotic agents used. <b><i>Methods:</i></b> We retrospectively reviewed cases involving colonoscopic polyp resection between September 2002 and December 2014. The risk of PPB was assessed according to patient and lesion factors, including antithrombotic use. Antithrombotics were discontinued before polypectomy. <b><i>Results:</i></b> A total of 6,382 colonoscopies with 12,876 polypectomies were analyzed. PPB occurred in 55 patients (0.9%) and 63 lesions (0.5%). Among patients treated with antithrombotics, heparin bridging (HB) therapy was an independent risk factor of PPB (per patient, 20%, OR 33.1, <i>p</i> &#x3c; 0.001; per lesion, 9.1%, OR 17.3, <i>p</i> &#x3c; 0.001) compared to those without antithrombotics (per patient 0.7%; per lesion 0.4%). Among patients without HB, the combination of anticoagulant + antiplatelet agents was significantly associated with PPB (per patient, 5%, OR 7.73, <i>p</i> = 0.007; per lesion, 2.4%, OR 6.31, <i>p</i> = 0.003). <b><i>Conclusion:</i></b> HB therapy is a major risk factor for PPB. Among patients without HB, anticoagulant + antiplatelet therapy was a significant risk factor for PPB.