The article reviews the role of low-dose aspirin in preventing atherosclerotic cardiovascular disease (ASCVD). Aspirin's mechanism of action involves the irreversible acetylation of serine-529 in platelet prostaglandin H synthase-1, which blocks cyclooxygenase (COX)-1 activity and reduces thromboxane A2 (TXA2) biosynthesis. This blockage is cumulative with repeated daily dosing, leading to a significant reduction in TXA2-dependent platelet activation. Clinical trials have shown that low-dose aspirin reduces the risk of coronary atherothrombosis and its recurrence, increases the risk of gastrointestinal bleeding from pre-existing mucosal lesions, and decreases the risk of sporadic colorectal adenoma recurrence. The article discusses the pharmacokinetics and pharmacodynamics of aspirin, highlighting its simple pharmacokinetics, lack of requirement for metabolic activation, and short half-life. The clinical efficacy of aspirin is supported by numerous placebo-controlled randomized trials, demonstrating its effectiveness in reducing the risk of vascular events in various patient populations. The safety profile of aspirin is also reviewed, including its gastrointestinal toxicity and potential for cognitive impairment. Additionally, the article explores the chemopreventive effects of low-dose aspirin against colorectal cancer, supported by observational studies, meta-analyses, and randomized controlled trials. The evidence suggests that aspirin's chemopreventive effect may be due to its ability to inhibit abnormal TXA2-dependent platelet activation at sites of intestinal mucosal injury. The article concludes by discussing the future of aspirin in antiplatelet therapy, noting that it is unlikely to be replaced by P2Y12 inhibitors due to their comparable efficacy and bleeding liability. It emphasizes the need for improved adherence and compliance with aspirin therapy, particularly in low-income countries, and highlights the potential of novel therapeutic targets and non-invasive biomarkers to enhance the balance of benefits and risks in primary prevention settings.The article reviews the role of low-dose aspirin in preventing atherosclerotic cardiovascular disease (ASCVD). Aspirin's mechanism of action involves the irreversible acetylation of serine-529 in platelet prostaglandin H synthase-1, which blocks cyclooxygenase (COX)-1 activity and reduces thromboxane A2 (TXA2) biosynthesis. This blockage is cumulative with repeated daily dosing, leading to a significant reduction in TXA2-dependent platelet activation. Clinical trials have shown that low-dose aspirin reduces the risk of coronary atherothrombosis and its recurrence, increases the risk of gastrointestinal bleeding from pre-existing mucosal lesions, and decreases the risk of sporadic colorectal adenoma recurrence. The article discusses the pharmacokinetics and pharmacodynamics of aspirin, highlighting its simple pharmacokinetics, lack of requirement for metabolic activation, and short half-life. The clinical efficacy of aspirin is supported by numerous placebo-controlled randomized trials, demonstrating its effectiveness in reducing the risk of vascular events in various patient populations. The safety profile of aspirin is also reviewed, including its gastrointestinal toxicity and potential for cognitive impairment. Additionally, the article explores the chemopreventive effects of low-dose aspirin against colorectal cancer, supported by observational studies, meta-analyses, and randomized controlled trials. The evidence suggests that aspirin's chemopreventive effect may be due to its ability to inhibit abnormal TXA2-dependent platelet activation at sites of intestinal mucosal injury. The article concludes by discussing the future of aspirin in antiplatelet therapy, noting that it is unlikely to be replaced by P2Y12 inhibitors due to their comparable efficacy and bleeding liability. It emphasizes the need for improved adherence and compliance with aspirin therapy, particularly in low-income countries, and highlights the potential of novel therapeutic targets and non-invasive biomarkers to enhance the balance of benefits and risks in primary prevention settings.