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Image-guided core-needle breast and axillary biopsy (CNB) is the standard-of-care procedure for the diagnosis of breast cancer. Although the risks of CNB are low, the most common complications include bleeding and hematoma formation. Post-procedural bleeding is of particular concern in patients taking antithrombotic therapy, but there is currently no widely established standard protocol in the United States to guide antithrombotic therapy management. In the face of an increasing number of patients taking antithrombotic therapy and with the advent of novel classes of anticoagulants, the American College of Radiology guidelines recommend that radiologists consider cessation of antithrombotic therapy prior to CNB on a case-by-case basis. Lack of consensus results in disparate approaches to patients on antithrombotic therapy undergoing CNB. There is further heterogeneity in recommendations for cessation of antithrombotic therapy based on the modality used for image-guided biopsy, target location, number of simultaneous biopsies, and type of antithrombotic agent. A review of the available data demonstrates the safety of continuing antithrombotic therapy during CNB while highlighting additional procedural and target lesion factors that may increase the risk of bleeding. Risk stratification of patients undergoing breast interventional procedures is proposed to guide both pre-procedural decision-making and post-procedural management. Radiologists should be aware of antithrombotic agent pharmacokinetics and strategies to minimize post-procedural bleeding to safely manage patients.