Aspirin (ASA) is the most commonly prescribed antiplatelet agent. Although the evidence for efficacy of aspirin for secondary prevention of ischemic events in patients with established cardiovascular disease is strong, its role in primary prevention has been subject of controversies over the past decades. In fact, historical trials have shown only modest benefit in terms of reduction of ischemic events, mostly myocardial infarction and to a lesser extent stroke, and only at the expense of an increased risk of bleeding. These observations have led to divergent recommendations from professional societies on the use of ASA for primary prevention of cardiovascular disease manifestations. However, recent results from three trials of primary prevention have shown either no benefit or modest benefit on combined ischemic end points, without any impact on hard cardiovascular events such as myocardial infarction or stroke, accompanied by an increased risk of bleeding. Overall, this translated into neutral net benefit or even harm with the use of aspirin in patients with no overt cardiovascular disease. These results have accordingly led to a downgrade in the current recommendations on the use of ASA for primary prevention. This article provides an overview on the current evidence on the use of aspirin for primary prevention of cardiovascular disease.