The increased rate of bleeding during and after cardiac procedures is a concern. The best strategy is prevention of bleeding complications with anticoagulant therapy that provides an adequate anti-thrombotic effect while reducing bleeding. The independent relationship between bleeding and blood transfusion and mortality among patients with coronary artery disease is reviewed. Findings suggest that in the modern era of percutaneous coronary intervention, prevention of bleeding should be a goal of therapy, which can be achieved while preserving the low rate of ischemic complications.