Myocardial infarction and stroke are still leading causes of death worldwide. The underlying pathology is atherosclerosis, which is considered to be orchestrated by inflammation and manifests by a build-up of plaque in the inner lining of arteries. Damage of an atherosclerotic plaque, by either plaque erosion or rupture, results in exposure of thrombogenic components to the bloodstream. This in turn triggers platelet activation and subsequent thrombus formation, a process called atherothrombosis. The overall aim of this thesis was to provide novel insights in the roles of platelets at the intersection of thrombosis and inflammation by developing and implementing state of the art methods. This thesis particularly focused on novel antithrombotic agents (and combinations thereof) to prevent secondary events with (athero)thrombosis as the underlying cause.