Patients with acute coronary syndromes (ACS) have high recurrent ischemic event rates despite management with current guideline-based therapies. Recombinant nematode anticoagulant protein (rNAP)c2 provides factor Xa-dependent inhibition of the tissue factor/factor VIIa complex acting proximally on the clotting cascade. It may be administered either intravenously or subcutaneously and has an elimination half-life of approximately 50-60 h. rNAPc2 reduces thrombin formation in patients undergoing elective percutaneous coronary interventions (PCI) and in patients with non-ST segment elevation ACS managed with an early invasive strategy, while bleeding rates are comparable with currently used anticoagulants. Patients receiving rNAPc2 undergoing emergent coronary artery bypass surgery within 96 h of dosing have increased rates of major bleeding. Some heparin coadministration may be necessary to avoid PCI-related thrombotic complications. Large-scale trials are needed to confirm these findings and to evaluate the impact of rNAPc2 on clinical events.