Thrombotic disorders are one of the most common causes of morbidity and mortality in developing and developed countries. Several well-known genetic traits underlie predisposition to venous thrombosis. In particular, high factor VIII levels are a risk factor for venous thrombosis and coronary artery disease (CAD). However, similar insight into the genetic component of arterial thrombosis predisposition has not materialized fully, despite considerable effort. The authors present an illustrative case of a 32-year-old Saudi Arabian patient with peripheral arterial thrombosis whose only identifiable risk factor were high factor VIII levels. We also provide a comprehensive review of the current state of knowledge concerning the role of high factor VIII levels in determining the risk of arterial thrombosis or ischemic heart disease (IHD). We conclude that high factor VIII levels are a risk factor for thrombosis, with a greater impact on venous than on arterial thrombosis. However, due to a lack of international consensus on methods for the laboratory testing of factor VIII levels in plasma, we would not currently recommend the measurement of factor VIII levels as part of routine thrombophilia screening.