Percutaneous coronary intervention (PCI) is one of the most common medical procedures performed for treatment of coronary artery disease. Antiplatelet medications as adjunctive therapy for PCI are used routinely, with indications for specific agents or their combinations varying depending on the clinical scenario. While the cost-effectiveness of well-established agents has been extensively studied, newer drugs have not been evaluated as thoroughly. In addition, the clinical application of some antiplatelet drugs has recently changed, thus making older studies of cost effectiveness less applicable to the current landscape of clinical practice. This article reviews cost-effectiveness considerations of antiplatelet therapies in the treatment of coronary artery disease in patients undergoing PCI. Aspirin, P2Y12 inhibitors including clopidogrel and the newer agents prasugrel and ticagrelor, as well as glycoprotein (GP) IIb/IIIa inhibitors, are discussed. Overall, the use of dual antiplatelet therapy with aspirin and a P2Y12 inhibitor in patients undergoing PCI improves ischaemic outcomes and appears to be cost effective. The few available studies suggest that the recently approved medications prasugrel and ticagrelor are cost-effective alternatives to clopidogrel. However, no direct comparison between these two newer agents is available. The indications for GP IIb/IIIa inhibitors have changed in the current PCI era, and there is a paucity of cost-effectiveness data for their use in contemporary care.