Abstract： Objective To investigate the impact of smoking on the efficacy of oral aspirin for stroke prevention in patients with mild to moderate carotid artery stenosis. Methods Included in this study were 300 patients with mild to moderate carotid artery stenosis treated in our hospital between August 2011 and March 2015. All the patients were given oral aspirin for stroke prevention. According to smoking habits,these patients were divided into non-smokers(n=94)and smokers(n=206). The smokers were further divided into mild smokers(n=88),moderate smokers(n=70)and heavy smokers(n=48)according to smoking index. Before and at 6,12 months of treatment,all the patients were evaluated with the National Institutes of Health Stroke Scale(NIHSS)score and modified Rankin score(mRS). The changes in carotid intima-media thickness(CIMT)were examined by carotic ultrasound screening. The number of patients with carotid intima thickening,or with plaque formation(as well as the plaque area)was recorded at 6 months of treatment. During a follow-up for 12 months,the incidence of stroke and the adverse hemorrhage events was recored. Results The carotic ultrasonography showed that non-smokers had less carotid intima thickening and plaque formation than the smokers at 6 months of treatment(all P<0.05). With the increase in smoking index,there was an increase in rates of carotid artery intima thickening and plaque formation. At 6 months of treatment,non-smokers had lower CIMT and smaller plaque areas than smokers(all P<0.05);While the CIMT was greater in moderate to heavy smokers than in mild smokers,and in heavy smokers than in moderate smokers(all P<0.05). There were no significant differences in NIHSS score and mRS among all patients before treatment(all P>0.05). At 6 and 12 months of treatment,the NIHSS score and mRS were significantly reduced in all groups(all P<0.05);and non-smokers had lower NIHSS score and mRS than smokers(all P<0.05). With the increase in smoking index,the reduction in NIHSS score and mRS appeared slower. The incidence rates of stroke in non-smokers,mild,moderate and heavy smokers were 14.9%(14/94), 28.4%(25/88),38.6%(27/70),and 45.8%(22/48),respectively. The incidence rate of stroke was higher in smokers than in non-smokers(all P<0.05),in heavy smokers than in moderate to mild smokers,and in moderate smokers than in mild smokers(all P<0.05). The incidence rate of cerebral hemorrhage in heavy and moderate smokers was higher than that in non-smokers(both P<0.05). Conclusion Smoking may interfere with the efficacy of aspirin for stroke prevention in patients with mild to moderate carotid artery stenosis ,and may increase the risk of stroke and the incidence of adverse events.