Thrombocytosis is frequently encountered as an incidental laboratory finding. The most common etiology is reactive (secondary) thrombocytosis due to infections, trauma, surgery, or occult malignancy. Even though thrombocytosis is benign and self-limiting in most cases, it can result in hemorrhage or thrombosis. The hypercoagulable state is characterized by episodes of thrombosis and can be due to inherited or acquired conditions. Extreme thrombocytosis may result in thrombotic events such as acute myocardial infarction, mesenteric vein thrombosis, and pulmonary embolism. It is important for physicians to be familiar with the complications associated with thrombocytosis. Postsplenectomy reactive thrombocytosis has an incidence of about 75% to 82%. Thrombosis in association with elevated platelet count after splenectomy is well recognized, with an incidence of approximately 5%. This case report describes a 61-year-old patient who underwent emergent splenectomy and presented 1 week later with acute ST segment elevation myocardial infarction. Severe thrombocytosis, which was not present prior to splenectomy, was noted, and a diagnosis of reactive thrombocytosis was initially made. Involvement of the right coronary artery led to emergent percutaneous transluminal coronary angioplasty. Essential thrombocytosis was considered when treatment with hydroxyurea failed to lower the platelet count. A review of arterial and venous thrombosis in patients with severe thrombocytosis is presented, and the approach to the management of such patients is discussed.