Context: Guided self-change (GSC) is theory-driven based on cognitive-behavioral change models such as transtheoreticlal model (TTM) and can be applied with nicotine replacement therapy (NRT) for behavioral change of smoking in chronic obstructive pulmonary disease (COPD) smokers. Aims: This study aimed to investigate the individual GSC, NRT, and GSC-NRT on smoking cessation of COPD patients. Settings and Design: This randomized clinical control trial study was carried out in Imam Khomeini Hospitals in Mazandaran province in 2016– 2017. Materials and Methods: Three-group block randomized controlled trial, comparing GSC (n = 20), NRT (n = 20), and GSC-NRT (n = 20) in smoking cessation and other related variables COPD smokers with follow‑ up to 29‑ week. Statistical Analysis Used: Descriptive statistics, Chi-square, and repeated measures ANOVA test were used to analyze the data. Results: The GEE model revealed that GSC reduced the odds of quitting smoking rate compared to the NRT group (odds ratio = 0. 31, 95% confidence interval: 0. 022– 0. 545, ES = 0. 20). Furthermore, the TTM questionnaire, the Fagerstrom test for nicotine dependence, and spirometry variables were evaluated in the three groups. The recovery in nicotine dependency, the exhaled carbon monoxide and spirometry variables was more pronounced in the GSC and GSC‑ NRT groups than in the NRT over 29 weeks after the treatments. Cons (PV = 0. 009, ES = 0. 52), pros (PV = 0. 04, ES = 0. 12), experiential process (PV = 0. 005, ES = 0. 18), counterconditioning (PV = 0. 04, ES = 0. 12), stimulus control (PV = 0. 004, ES = 0. 19), environmental‑ reevaluation (PV = 0. 0001, ES = 0. 30), and habitual craving (PV = 0. 004, ES = 0. 19) were significant across the three groups. Conclusion: The interventions in the GSC and combined GSC-NRT groups were significantly more effective than in the NRT group in TTM variables, and GSC and combined GSC-NRT were equally effective in smoking cessation rate.