Warfarin is clinically used as the first choice for long-term anticoagulant therapy, and for the prevention of thromboembolic events. However, when used at low doses in the long term or high doses in the short term, warfarin treatment may result in tissue calcifications-such as calcifications in the coronary arteries, peripheral vascular system, blood vessels of patients with atrial fibrillation and chronic kidney disease, and vascular valves-and atherosclerotic plaque calcification. These warfarin-induced calcifications may affect cardiovascular function and exacerbate diseases such as diabetes and hypertension. Studies have shown that quercetin, osteoprotegerin, sclerosin, and sodium thiosulfate may alleviate these effects by interfering in the Wnt/β-catenin, TG2/β-catenin, Bone Morphogenetic Protein 2 (BMP2), and Eicosapentaenoic Acid/Matrix Metallopeptidase-9 (EPA/MMP-9) pathways, respectively. Nevertheless, the mechanism underlying warfarin-induced calcification remains unknown. Therefore, the question as to how to effectively attenuate the calcification induced by warfarin and ensure its anticoagulant effect remains an urgent clinical problem that needs to be resolved. To utilize warfarin rationally and to effectively attenuate the calcifications, we focused on the clinical phenomena, molecular mechanisms, and potential strategies to prevent calcification. Highlighting these aspects could provide new insights into the effective utilization of warfarin and the reduction of its associated calcification effects.