Coronary heart disease is the number one cause of death in the world and acute coronary syndromes (ACS) continue to be associated with high rates of morbidity. ACS refers to the spectrum of acute myocardial ischemia, including unstable angina, ST segment elevation myocardial infarction (STEMI), and acute MI without ST segment elevation (NSTEMI). Current guidelines indicate both aspirin and glycoprotein IIb/IIIa receptor antagonists (if catheterization/revascularization are planned) as class IA recommendations in ACS. Anticoagulant therapy, in the form of heparin, is a class IA recommendation for the acute hospital phase of ACS. The risk of recurrent thrombotic events following ACS remains high in the post-hospital phase, creating a rationale for the use of oral direct thrombin inhibitors such as ximelagatran, in both the acute and long-term settings. The Efficacy and Safety of the Oral Direct Thrombin Inhibitor Ximelagatran in Patients with Recent and Myocardial Damage (ESTEEM) trial, a placebo-controlled, double-blind study of post-MI patients, evaluated 4 dosing regimens of ximelagatran versus placebo in the initial months following an ACS and found an encouraging reduction in the end points of death, MI, and stroke with the use of an oral direct thrombin inhibitor.