Bleeding events significantly worsen the prognosis of patients, increasing mortality by up to seven times. The use of antithrombotic therapy in patients undergoing percutaneous coronary intervention reduces ischemic events but significantly increases the risk of bleeding. While drug-eluting stents have decreased the rate of late and very late stent thrombosis, this complication is still feared following stent implantation due to a high mortality, which ranges from 5% to 45%. Moreover, many factors related to the patient’s clinical condition contribute to the increased risk of both bleeding and ischemia. Therefore, shortening the dual antiplatelet therapy without significantly increasing the risk of ischemic events in the group of patients at high risk of bleeding seems to be crucial for improving their prognosis. Drug-coated balloons allow for the delivery of antiproliferative drugs directly into the vessel wall without the need for a metal stent platform implantation. This approach decreases the risk of thrombosis, suggesting that it may be appropriate to shorten the duration of dual antiplatelet therapy following drug-coated balloon treatment. This chapter will summarize the data regarding the use of single antiplatelet therapy in patients who are at high risk of bleeding after drug-coated balloon procedures.