Purpose Cold snare polypectomy (CSP) is a safe and effective method for removing colonic polyps ≤10 mm in size. However, there is uncertainty about whether the cardiovascular risk of discontinuing antithrombotic medications before CSP outweighs the risk of intraoperative and post-polypectomy bleeding. The aim of this systematic review was to study the safety of CSP in patients on continued antiplatelet (thienopyridine) therapy. Methodology In accordance with the PRISMA guidelines, a search of MEDLINE, CENTRAL and EMBASE databases was conducted. The primary outcome was clinically significant post-polypectomy bleeding (within 30 days). Secondary outcomes were intraoperative bleeding and thromboembolic events. Results 6 studies, including 2 RCTs, 1 prospective cohort study and 3 retrospective cohort studies were included. Studies had heterogenous inclusion criteria, methodology and reported outcomes. The rate of clinically significant post-polypectomy bleeding was 0.72% in the thienopyridine group vs 0.22% in the aspirin only group. Intraprocedural bleeding was slightly increased in the thienopyridine group (11.73% vs 6.58%). Due to a paucity of data, thromboembolic risk is likely statistically insignificant. Conclusion Initial data analysis shows a slightly increased rate of clinically significant post-polypectomy bleeding in the thienopyridine group as well as a slightly increased rate of intra-procedural bleeding. Despite the increased risk, the incidence of these bleeding complications is still low, while there is evidence to suggest the risk of thromboembolism increases significantly when thienopyridines are ceased. Therefore, endoscopists must consider whether the bleeding risk outweighs the risk of cardiovascular events in the perioperative period.