Thrombocytosis is a frequent laboratory finding but not a diagnosis. Therefore, elevated platelet counts (>450 x 10(9)/1) require careful diagnostic work-up to differentiate between reactive thrombocytosis (RT), caused by various conditions, and essential thrombocythemia (ET), a myeloproliferative neoplasm (MPN). In either setting, aspirin is widely used in clinical practice. However, RT (even at platelet counts >1000 x 10(9)/1) has never been shown to cause thrombosis or bleeding due to acquired von Willebrand factor defects in association with high platelet counts. Identification of reactive conditions and appropriate therapy of the underlying disorder are most relevant. By contrast to RT, ET and related MPN can be associated with thrombosis and/or hemorrhage. Current recommendations suggest the use of low-dose aspirin in all patients with ET unless contraindicated. However, the strength of this recommendation is weak, i.e. evidence level Ilb grade B.A potential benefit of aspirin used for primary thromboprophylaxis in ET is mostly derived from the ECLAP study in polycythemia vera (PV). However, translating study results from PV to ET appears to be highly questionable and may be biased. In the absence of robust data regarding the benefit-risk balance of aspirin in ET, it appears reasonable (1) to stratify patients according to their individual thrombotic and bleeding risk, (2) to restrict the use of aspirin to high-risk categories and patients with microcirculatory disturbances, (3) to test for pharmacological efficacy (COX-1 inhibition; measurement of TXB2), and (4) to modify the aspirin dosing regimen (twice instead of once daily) if required.