Reliable anticoagulation is a cornerstone for percutaneous coronary intervention (PCI), with most interventional cardiologists achieving this using unfractionated heparin and bivalirudin. The ACUITY [ ] and HORIZONS-AMI trials [ ] led to the widespread adoption of bivalirudin for anticoagulation in the setting of PCI for acute coronary syndrome (ACS). The reliability of anticoagulation and ease of administration for bivalirudin are extremely appealing and can help reduce the complexity sometimes associated with frequent monitoring of activated clotting time required with unfractionated heparin administration, especially in complicated ST elevation myocardial infarction cases. One of the major benefits of bivalirudin was the reduction of major bleeding when compared with unfractionated heparin. The decision to proceed with heparin versus bivalirudin may also be driven by the need for glycoprotein (GP) IIb/IIIa inhibitor use if the initial angiogram demonstrates severe clot burden or in situations where antiplatelet therapy is lacking, as GP IIb/IIIa inhibitors should only be used as bailout therapy with bivalirudin due to increased bleeding risk. However, the subsequent EUROMAX [ ] and HEAT-PPCI trials [ ] signaled an increased risk of acute stent thrombosis following PCI in patients with ACS. Subsequent meta-analyses confirmed that anticoagulation with bivalirudin when compared with unfractionated heparin was associated with an increased risk of stent thrombosis, though both access-site and non-access-site major bleeding are reduced with bivalirudin [ ]. These data led to a change in the 2018 European Society of Cardiology Guidelines [ ] and, subsequently, the 2021 ACC/AHA/SCAI (American College of Cardiology/American Heart Association/Society for Cardiovascular Angiography and Interventions) Guideline for Coronary Artery Revascularization recommending preference for unfractionated heparin for PCI, with bivalirudin falling to a Class of Recommendation 2B, suggesting bivalirudin may be a reasonable alternative to unfractionated heparin to reduce bleeding [ ].