In 2008, we published our chest pain protocol for the management of acute coronary syndromes (ACS) and acute myocardial infarction. Our algorithm was specifically designed for our institution, which includes primary percutaneous intervention (PCI) for all ST-elevation myocardial infarctions (STEMIs) and a preferred invasive approach for non-STEMIs. Since 2008, there have been changes in the adjunctive pharmacotherapeutic armamentarium for PCI in both the STEMI and non-STEMI ACS context. In particular, recent data on the novel antiplatelet agent prasugrel, dosing of clopidogrel after PCI, and interactions with clopidogrel and other medicines and substrates, which can lead to decreased platelet response to clopidogrel, have led us to update our ACS clinical pathway. We present our updated chest pain algorithm with a brief review of the rapidly evolving changes in adjunctive pharmacotherapy for PCI, and provide rationale for the changes that we have made to our institutional protocol. Clinical pathways need to be regularly updated and revised by incorporating new evidence from clinical trials to ensure optimal clinical care.