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Although aspirin has a well-established role in preventing adverse events in patients with known cardiovascular disease (CVD), its benefit in patients without a history of CVD remains under scrutiny. Current data have provided insight into the risks of aspirin use, particularly bleeding, compared with its benefits in primary CVD prevention. Although aspirin is inexpensive and widely available, especially in developing countries, there is lack of evidence that the benefits outweigh the adverse events with continuous aspirin use in primary CVD prevention. Therefore, the decision to initiate aspirin therapy should be an individual clinical judgment that weighs the absolute benefit in reducing the risk of a first cardiovascular event against the absolute risk of major bleeding, and tailored to the patient's CVD risk. This risk must be calculated, based on accurate and cost-benefit locally developed risk assessment tools, the most discriminating threshold be identified. Additionally, patients preferences should be taken into account when making the decision to initiate aspirin therapy in primary prevention of CVD or not. Physicians should continuously be trained to calculate their patients CVD risk, and concomitant strategies be emphasized.