Randomized controlled trials comparing the effects of aspirin for primary prevention of CVD versus control and including at least 1000 patients were eligible for this meta-analysis. The primary efficacy outcome was all-cause mortality. Secondary outcomes included cardiovascular mortality, major adverse cardiovascular events (MACE), myocardial infarction, ischemic stroke, and net clinical benefit. The primary safety outcome was major bleeding. Subgroup analyses involving sex, concomitant statin treatment, diabetes, and smoking were performed. Acetylsalicylic acid (commonly referred to as “aspirin”) is an antithrombotic agent that inhibits platelets by irreversibly acetylating the serine residue of cyclooxygenase-1 (COX-1) in platelets with subsequently reduced levels of prothrombotic thromboxane A2 (TxA2). In patients with known cardiovascular disease (CVD), the potential for aspirin to reduce further cardiovascular (CV) events significantly outweighs the risks of major bleeding and thus aspirin has since become a mainstay in secondary prevention of CVD. However, in primary prevention, its role is still under debate. This is due to an as yet unclear balance between the benefits and risks of aspirin treatment in patients without a diagnosed atherosclerotic disease.