The number of patients who undergo percutaneous coronary intervention (PCI) and additionally require chronic anticoagulation for a variety of indications is not insignificant. The choice of antithrombotic therapy after PCI in patients with chronic indications for anticoagulation therapy remains a challenge for interventional cardiologists, as the risk of bleeding must be adequately weighed against the benefit of preventing future ischemic events. While these clinical scenarios are encountered in approximately 10 % of patients undergoing PCI, current practice guidelines do not sufficiently guide physicians as to how to best treat these PCI patients requiring chronic anticoagulation. Notwithstanding the clinical difficulties of treating such patients, there are several recent studies and analyses that have assessed optimal antithrombotic strategies in the PCI population, and there are several others that are currently underway. This review evaluates the currently available data and clinical scenarios commonly encountered by treating physicians.