BACKGROUND: Individuals are faced with numerous stressful life events which can negatively influence mental health. Many individuals use smoking as a means of confronting stress. Given the relatively high prevalence of smoking in central Iran, the present study was conducted to compare stress levels in smokers, non-smokers and those who had quit smoking. METHODS: This study was conducted as part of Isfahan Cardiovascular Research Program on 9752 individuals in the cities of Isfahan, Arak, and Najafabad in 2008. Sampling was performed using multi-stage cluster randomization method. Data on age, sex, demographic characteristics, and smoking status was collected through interviews. Stress level detected by General Health questionnaire.Logistic regression and chi- squere test was used for data analyzing. RESULTS: In the present study, 30% of non-smokers, 32.1% ex- smoker and 36.9% of smokers had GHQ of 4 and higher (P = 0.01). In regression analysis, the final model which was controlled for age, sex, socioeconomic statues (including place of residence, marital status and education level) showed that the odds ratio of stress in smokers and ex- smoker was significantly higher than in non-smokers (OR = 1.66 and OR = 1.12, respectively). CONCLUSION: Since in conducted studies, mental problems and stresses have had an important role in people’s smoking, it seems suitable to use the results of this study to present intervention for correct methods of coping with stress towards reducing the prevalence of smoking in the community.Keywords: Cigarette, Stress, Community-based Program.