The present chapter evaluates the benefit of aspirin in primary prevention. Aspirin is considered as molecule of last century. Aspirin has been considered to be beneficial in reducing the risks of cardiovascular diseases with remarkable impact on outcome of CVD. The role of aspirin for secondary prevention is well proven. For the primary prevention, risk benefit ratio should be assessed for individual patient. It is recommended for high-risk patients. The chapter marks important points on the aspirin for primary prevention in specific populations such as diabetics, impact of gender, stroke prevention and the optimal dose and preparation of aspirin with summary of recommendations on prophylactic aspirin use imposed by various organizations such as American Heart Association, European Stroke Organization, United States Preventive Services Task Force, European Society of Cardiology and Joint British Societies.