Objective: To determine the smoking cessation rates of outpatients with cardiopulmonary disease and the differences between non-cardiopulmonary diseases. Materials and Methods: Two hundred and two active smokers with comorbid diseases were prospectively evaluated between September 2004 and January 2008 in this observational study. All of the patients answered Fagerstrom test for nicotine dependence with a regular questionnaire of general characteristics. Behavioral counseling therapies were administered to all of the subjects. Nicotine replacement therapy, bupropion or combination therapies were the pharmacological therapies after running the baseline spirometry and carbon monoxide oximetry tests. Subjects were classified as patients with cardiopulmonary disease (124) and non-cardiopulmonary diseases (78), based on medical history. Student t and Chi-square tests were used for statistical analyses. Results: The age of smoking was similar but total amount of smoked tobacco was higher (p<0.05) in the cardiopulmonary diseases group. In this group, the main smoking cessation reason was the existing disease (51%) (p<0.05). There was no other significant difference between two groups including treatment protocols. The smoking cessation rates were less (40%) with high relapses (12%) in cardiopulmonary diseases group (p<0.01 and p=0.01 respectively). In the subgroup analysis, treatment procedures were equivalent (p>0.05). Conclusion: Results of this analysis confirm that, tobacco dependence is still a severe but necessary condition for the patients with cardiopulmonary diseases. Additionally neither of the treatment protocols was superior to the others.