Abstract Antiplatelet agents and anticoagulants make up the larger group of antithrombotic medications, which have seen increasing use worldwide as populations in developed countries age, and ischemic heart disease prevalence rises. Antithrombotic medications reduce the risk of thromboembolic events in susceptible individuals, but increase the risk of gastrointestinal bleeding. Cessation of antithrombotic drugs prior to endoscopic therapy has been proposed, aimed at reducing the risk of immediate and early bleeding. However, interruption of antithrombotic therapy is associated with cardiovascular risk. The peri-endoscopic management of patients at high thromboembolic risk therefore requires knowledge of both the bleeding risk associated with endoscopic procedures, and the potential risks of stopping antithrombotic therapy. Three major endoscopy organizations (British Society of Gastroenterology, American Society of Gastrointestinal Endoscopy & European Society of Gastrointestinal Endoscopy) have published guidelines aimed at providing a rational strategy for the endoscopist in managing the individual patient on antithrombotic medication. This article compares and contrasts the approach of each guideline, in an attempt at consensus. The British Society of Gastroenterology and American Society of Gastrointestinal Endoscopy guidelines address the use of both antiplatelet agents and anticoagulants during the peri-endoscopic period, while the European Society of Gastrointestinal Endoscopy guideline is focused solely on antiplatelet medication. The guidelines were formulated with reference mainly to observational studies and expert opinion, and therefore have a limited basis in evidence. A rational strategy is proposed for common scenarios encountered in gastrointestinal endoscopy, based on the published guidelines. Despite the existence of these guidelines, they serve at best as a framework for individualized management tailored to the patient’s particular clinical scenario.