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Introduction Type 2 diabetes mellitus (T2DM) is a common metabolic disorder, which carries a risk for atherosclerosis and cardiovascular impairment. The purpose of this review is to demonstrate the role of acetylsalicylic acid (ASA) in primary cardiovascular prevention in T2DM patients, as well as present an outline of microRNAs (miRNA) relevant to ASA therapy and should be evaluated as targets to improve treatment. Brief description of state of knowledge Although the etiology of hypercoagulable state in T2DM is considered multifactorial, attention mainly focuses on platelet disturbances. Platelets in T2DM not only demonstrate intensified adhesion, activation, aggregation, and thrombin generation, but are likely to deliver miRNAs at specific sites of action in the cardiovascular system, hence contributing to the pathogenesis of cardiovascular events. Objective Since cardiovascular disease (CVD) is currently the leading cause of mortality among T2DM patients, appropriate risk stratification and management is necessary to reduce morbidity and mortality in this group. A large number of T2DM patients show inadequate response to antiplatelet therapy, which currently revolves around ASA, despite compliance with treatment regimens proposed by the guidelines. Conclusions The review shows that the use of ASA for primary prevention is beneficial in patients at high cardiovascular risk. However, it is important to select patients in whom ASA therapy will bring the most beneficial outcome with minimal risk for adverse effects. This can be potentially achieved with the use of unique biomarkers. The biologically diverse characteristics of miRNA make them a promising novel biomarker and potential tool for better risk stratification, as well as antiplatelet therapy optimization.