Essential thrombocythemia (ET) is an acquired clonal hematological stem-cell disorder that is characterized by a persistent increase in platelet count over 600,000/microl and elevated megakaryocyte levels in the bone marrow. Patients with ET are on the one hand at risk of thrombosis and on the other hand of hemorrhagic events especially in patients with very high platelet accounts. We report two illustrative cases with ET and acute coronary syndrome from our recent clinical experience illustrating the challenges in the antithrombotic treatment of these patients.