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Objective: Behcet's disease (BD) is an inflammatory disease and smoking may have a role in its triggering. This case-control study was conducted to investigate the association between smoking and the risk of BD. Methods: We included 192 patients with BD and 822 healthy siblings of patient with BD and 373 healthy unrelated persons as control groups. Demographic data and smoking history of patients and their siblings were obtained by direct and in some cases by telephone interview with the participants. Demographic data and smoking history of healthy controls were obtained by direct interview. Propensity score matching (PSM) analyses for reducing the heterogeneity between studied groups and calculating the actual effect of smoking in BD was performed. Matching was performed based on demographic characteristics (age, gender, educational status and marital status). After PSM, we carried out multivariate analyses with BD as the main outcome variable and smoking history as the main predictor variable to calculate odds ratios with 95% confidence intervals. Results: Ever smoking was not significantly associated with an increased risk of BD compared with never smoking. In comparison with healthy siblings and healthy unrelated persons, the relative risk of developing BD was 0.8-2.6. No significant differences were observed in the clinical manifestations of BD patients in ever smokers and never smokers. However, disease activity in ever smokers at disease presentation was significantly more than never smokers. Conclusion: Smoking is not a significant risk factor for BD. [ABSTRACT FROM AUTHOR]