Cigarette smoking significantly contributes to atherosclerosis and atherothrombosis through endothelial dysfunction, inflammation, and thrombosis. Smoking induces endothelial dysfunction by reducing nitric oxide availability, increasing superoxide anion production, and enhancing endothelin release. This dysfunction leads to impaired vascular dilation and hemostasis regulation. Chronic inflammation in the vascular wall is a central mechanism of smoking-induced atherosclerosis, with damage-associated molecular patterns (DAMPs) and pattern recognition receptors playing key roles. Smoking also activates the NLRP3 inflammasome, cGAS-STING pathway, and Toll-like receptor 9, amplifying inflammatory cytokine expression. Smoking-induced oxidative stress and inflammation promote platelet adhesion, aggregation, and coagulation, contributing to thrombus formation. Matrix metalloproteinases (MMPs) further enhance plaque vulnerability and atherothrombotic events. Smoking exacerbates atherothrombosis by increasing inflammation, adhesion molecule expression, and MMP activity. The interplay between endothelial dysfunction, inflammation, and thrombosis highlights the need for smoking cessation to protect cardiovascular health. Understanding these mechanisms is crucial for developing effective interventions against smoking-related cardiovascular diseases.Cigarette smoking significantly contributes to atherosclerosis and atherothrombosis through endothelial dysfunction, inflammation, and thrombosis. Smoking induces endothelial dysfunction by reducing nitric oxide availability, increasing superoxide anion production, and enhancing endothelin release. This dysfunction leads to impaired vascular dilation and hemostasis regulation. Chronic inflammation in the vascular wall is a central mechanism of smoking-induced atherosclerosis, with damage-associated molecular patterns (DAMPs) and pattern recognition receptors playing key roles. Smoking also activates the NLRP3 inflammasome, cGAS-STING pathway, and Toll-like receptor 9, amplifying inflammatory cytokine expression. Smoking-induced oxidative stress and inflammation promote platelet adhesion, aggregation, and coagulation, contributing to thrombus formation. Matrix metalloproteinases (MMPs) further enhance plaque vulnerability and atherothrombotic events. Smoking exacerbates atherothrombosis by increasing inflammation, adhesion molecule expression, and MMP activity. The interplay between endothelial dysfunction, inflammation, and thrombosis highlights the need for smoking cessation to protect cardiovascular health. Understanding these mechanisms is crucial for developing effective interventions against smoking-related cardiovascular diseases.