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Background and purpose: to investigate the relationship between active cigarette smoking and the occurrence of extracranial (ECAS) and intracranial atherosclerotic stenosis (ICAS).Methods: We analyzed patients enrolled in the Chinese Intracranial atherosclerosis (CICAS), which was a prospective, multicenter, hospital-based cohort study. Smoking status was classified into never, former and current smoking. ICAS was evaluated with 3-dimentional time-of-flight MRA and ECAS was evaluated with cervical ultrasonography or contrast-enhanced MRA. Multivariable Logistic regression was performed to identify the association between smoking status and the occurrence of ECAS and ICAS.Results: A total of 2656 patients (92.7%) of acute ischemic stroke and 208 (7.3%) of transient ischemic attack were analyzed. The mean age was 61.9±11.2 and 67.8% were male. There were 141 (4.9%) patients had only ECAS, 1074 (37.5%) had only ICAS, and 261 (9.1%) had both ECAS and ICAS. Current smoking was significantly associated with the occurrence of ECAS (adjusted OR=1.47, 95% CI=1.09-1.99, P<0.01). In addition, with one year of smoking increment, the risk of ECAS increased by 1.1% (adjusted OR=1.011; 95% CI=1.003-1.019; P=0.005); with one cigarette smoked per day increment, the risk of ECAS increased by 1.0% (adjusted OR=1.010; 95% CI=1.001-1.020; P=0.03); and with one pack year of smoking increment, the risk of ECAS increased by 0.7% (adjusted OR=1.007; 95% CI=1.002-1.012; P<0.01). However, no similar significant association was found between smoking status and the occurrence of ICAS.Conclusion: A paradoxical dose-response relationship between cigarette smoking and the occurrence of ECAS and ICAS was identified. Further studies on molecular mechanisms were warranted.