This chapter about antithrombotic therapy during percutaneous coronary intervention (PCI) is part of the seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy: Evidence Based Guidelines. Grade 1 recommendations are strong and indicate that the benefits do, or do not, outweigh risks, burden, and costs. Grade 2 suggests that individual patients’ values may lead to different choices (for a full understanding of the grading, see Guyatt et al, CHEST 2004;126:179S–187S). Among the key recommendations in this chapter are the following: For patients undergoing PCI, we recommend pretreatment with aspirin, 75 to 325 mg (Grade 1A). For long-term treatment after PCI, we recommend aspirin, 75 to 162 mg/d (Grade 1A). For long-term treatment after PCI in patients who receive antithrombotic agents such as clopidogrel or warfarin, we recommend lower-dose aspirin, 75 to 100 mg/d (Grade 1C+). For patients who undergo stent placement, we recommend the combination of aspirin and a thienopyridine derivative (ticlopidine or clopidogrel) over systemic anticoagulation therapy (Grade 1A). We recommend clopidogrel over ticlopidine (Grade 1A). For all patients undergoing PCI, particularly those undergoing primary PCI, or those with refractory unstable angina or other high-risk features, we recommend use of a glycoprotein (GP) IIb-IIIa antagonist (abciximab or eptifibatide) [Grade 1A]. In patients undergoing PCI for ST-segment elevation MI, we recommend abciximab over eptifibatide (Grade 1B). In patients undergoing PCI, we recommend against the use of tirofiban as an alternative to abciximab (Grade 1A). In patients after uncomplicated PCI, we recommend against routine postprocedural infusion of heparin (Grade 1A). For patients undergoing PCI who are not treated with a GP IIb-IIIa antagonist, we recommend bivalirudin over heparin during PCI (Grade 1A). In PCI patients who are at low risk for complications, we recommend bivalirudin as an alternative to heparin as an adjunct to GP IIb-IIIa antagonists (Grade 1B). In PCI patients who are at high risk for bleeding, we recommend that bivalirudin over heparin as an adjunct to GP IIb-IIIa antagonists (Grade 1B). In patients who undergo PCI with no other indication for systemic anticoagulation therapy, we recommend against routine use of vitamin K antagonists after PCI (Grade 1A).