Antithrombotic management after percutaneous coronary intervention is based on dual antiplatelet therapy (DAPT), that has unequivocally shown to reduce the risk of recurrent ischemic events at cost of an important risk of bleeding. In order to balance ischemic and bleeding risks, DAPT duration should be based on patients and lesions features as well as stent type. Based on these considerations, patients at high bleeding risk (HBR) undergoing PCI represent a challenging subgroup. The Synergy stent (Boston Scientific, Marlborough, MA, USA) is a new-generation everolimus-eluting stent with a biodegradable polymer coating, presenting several features that have the potential to reduce acute and long-term thrombogenicity and the subsequent need for DAPT. The aim of this manuscript is to review the evidence about the impact of stent design on the optimal antithrombotic strategy in HBR patients and the potential role of the Synergy BP-EES in this relevant population.