BACKGROUND: Relapse is by far the most likely outcome of any smoking cessation attempt. The present study aimed to assess the effectiveness of cognitive-behavioral intervention based on Marlatt's model on relapse prevention of people who smoke. METHODS: This interventional study was conducted among 265 people who smoke who referred to smoking cessation centers in Kurdistan province in Iran (intervention group = 129, control group = 136). The intervention group received cognitive behavioral therapy smoking cessation based on the Marlatt's model for 8 sessions and each session was one hour weekly, and the control group received routine smoking cessation treatment trough 7 one-hour weekly sessions. The data were collected by using a researcher-made questionnaire. The follow-ups were performed immediately, 1 week and 3 months after the intervention. RESULTS: We found that 42.6% of the intervention group consumed more than 20 cigarettes daily before the intervention, reaching to 13.7% immediately, 10.2% one week and 6.2% three months after the intervention. There was a significant difference in the mean scores of internal and external high-risk situations, internal and external self-efficacy, coping skills, positive and negative outcome expectations, and abstinence violation effect between the intervention and control groups at immediately, one week, and three months after the intervention (P <
0.0001). A significant difference between the lapse and relapse rate in the intervention group compared to the control group immediately, one week and three months after the intervention was observed (P <
0.001). CONCLUSION: Cognitive-behavioral intervention is effective in reducing cigarette smoking, high-risk situations of smoking, abstinence violation effect, positive outcome expectation of smoking lapse and relapse and increasing self-efficacy, coping skills, and quitting smoking.