Chronic left ventricular systolic dysfunction is a well recognized problem with an increasingly significant impact on healthcare in the form of congestive heart failure (CHF). Advances in medicine have led to improved survival after myocardial infarction (MI) and as a result, an increased prevalence of left ventricular systolic dysfunction. An increased incidence of thromboembolism, especially stroke, in patients with left ventricular systolic dysfunction is also well recognized. Pharmacological strategies to prevent stroke have been proposed in numerous studies. For example, anticoagulation in patients with atrial fibrillation and heart failure has been shown to reduce mortality rates and the incidence of stroke; however, its role in patients with left ventricular dysfunction and normal sinus rhythm is unclear and utilization of anticoagulation in these patients varies widely. The role of aspirin to prevent thromboembolism in patients with CHF is controversial. The relatively new pharmacological agent ximelagatran, which has an advantage of unmonitored oral administration has the potential to change the anticoagulation strategy in patients with heart failure. Important trials to define optimal therapy for reducing the risk of thromboembolism and death in patients with left ventricular systolic dysfunction and sinus rhythm include the recently reported WATCH (Warfarin and Antiplatelet Therapy in Chronic Heart failure) trial and the WARCEF (Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction) trial, which is currently underway. The WATCH trial failed to outline significant differences between aspirin (acetylsalicylic acid), warfarin, and clopidogrel in the primary composite endpoint of all-cause mortality, nonfatal MI, and nonfatal stroke. Combined data from WATCH and WARCEF may provide sufficient statistical power to clarify outcomes such as stroke and death in patients with reduced cardiac ejection fraction. The pooled data may also help define optimal preventative measures for thromboembolism in patients with left ventricular systolic dysfunction and sinus rhythm.