Background: Smoking cessation is a key intervention for all smokers with chronic obstructive pulmonary disease (COPD). Poor treatment adherence is a challenge in clinical practice that might contribute to the lower efficacy of medication (eg, oral drug). However, it is unclear what factors will influence adherence among smokers with COPD. Methods: This study was based on an open-label randomized controlled trial (RCT) of varenicline and bupropion for smoking cessation among patients with COPD in China. The medication was given for 12 weeks, and visits and assessments were conducted at weeks 0, 1, 2, 4, 6, 9, 12, and 24. We assessed whether the adherence to smoking cessation treatment affects the smoking cessation efficacy and evaluated predictors of adherence. Results: A total of 136 participants were recruited from February 2019 to June 2020, and analyzed using the intention-to-treat (ITT) method. In this study, 48.5% (66/136) of the total participants had good adherence to smoking cessation, and good adherence significantly improved the efficacy of smoking cessation (OR=9.60, 95% CI 4.02-22.96, P < 0.001). After adjusting for age, gender, nationality, education, and marital status, we found older age, higher education level, having more previous quitting attempts, stronger self-efficacy and preparation in quitting smoking, recognizing hazards of smoking, longer duration of COPD, and higher St. George's Respiratory Questionnaire (SGRQ) scores were relevant to good adherence (P < 0.05). Conclusion: To our best knowledge, this is the first study to evaluate adherence to smoking cessation treatment among patients with COPD in China. Our study found that good adherence to smoking cessation treatment significantly improved the smoking cessation efficacy, and predictors of adherence were evaluated. We call on the medical community to pay attention to the adherence to smoking cessation among patients with COPD.