Patients with long-term oral anticoagulation are exposed to high bleeding risk and should be managed with care for invasive procedure. Angioplasty is assumed to increase bleeding and access site complications and it is often recommended to temporarily interrupt anticoagulation therapy. Moreover, due to the lack of recommendations, antithrombotic regimen adopted after stenting represents a substantial challenge for the physician who must balance the risk of ischemic and bleeding events. Nevertheless, approaches as uninterrupted therapeutic oral anticoagulation, transradial approach and a best knowledge of ischemic risk, haemorrhage risk and restenosis risk can limit long term complication. Herein, we review the currently available data assessing angioplasty and long-term antithrombotic therapy for stented patients with long-term oral anticoagulation and we propose a potential treatment paradigm to improve long-term prognosis.