Cardiovascular diseases, including acute coronary syndromes, are a major cause of death among tobacco smokers. Epidemiological studies have demonstrated that long‑term prognosis is worse in smokers with acute coronary syndromes than in nonsmokers. However, some studies have suggested that clopidogrel‑treated active smokers have better in‑hospital and short‑term follow‑up outcomes, a phenomenon regarded as the smoker's paradox. The smoker's paradox may be due to enhanced platelet response to clopidogrel therapy in active smokers as compared with nonsmokers caused by hepatic cytochrome P450 activation resulting in an increased generation of clopidogrel active metabolite. Another paradox has been reported after smoking cessation. Smoking cessation in clopidogrel‑treated patients after percutaneous coronary intervention is associated with increased platelet reactivity and a greater risk of high platelet reactivity. The smoking cessation paradox may increase the risk of thrombotic complications in patients treated with clopidogrel. More potent P2Y12 inhibitors may be considered in selected patients who stopped smoking after percutaneous coronary intervention. Further studies are required to determine the optimal antiplatelet strategy for stented patients who effectively quit smoking during clopidogrel treatment. The aim of this review is to discuss the risk of smoking and the potential elevated thrombotic risk related to smoking cessation.