Acute coronary syndromes (ACS) are associated with high rates of morbidity and mortality. The advances of antiplatelet and anticoagulation therapy over several years time have resulted in improved in cardiac outcomes, but with increased health care costs. Multiple cost-effectiveness studies have been performed to evaluate the use of available antiplatelet agents and anticoagulation in the setting of both ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation acute coronary syndrome (NSTE-ACS). Early on, the use of glycoprotein IIb/IIIa receptor inhibitors (GPIs) proved to be economically attractive in the management of ACS; however, the introduction of P2Y12 receptor antagonists limited their use to a bail out agents in complex interventions. Generic clopidogrel is probably still an economically attractive P2Y12 receptor antagonist choice, especially in low-risk ACS, while both ticagrelor and prasugrel present an economically attractive alternative option, especially in high-risk ACS and patients at risk for stent thrombosis. While enoxaparin presents an economically dominant alternative to heparin in NSTE-ACS, its role in STEMI in the contemporary era is unclear. During percutaneous coronary intervention (PCI), bivalirudin monotherapy was shown to be an economically dominant alternative to the combination of heparin and GPI in ACS. However, new studies may suggest that using heparin monotherapy may offer an attractive alternative. The comparative and cost effectiveness of different combinations of antiplatelet and antithrombotic therapy will be the focus of future expected clinical and economic assessments.