OBJECTIVES: We aimed to estimate the long-term (cost-)effectiveness of smoking cessation interventions for patients with chronic obstructive pulmonary disease (COPD). METHODS: A systematic review was performed for randomized controlled trials on smoking cessation interventions in COPD patients reporting the 12-month biochemical validated abstinence rates. The different interventions were grouped into four categories: usual care, minimal counseling, intensive counseling and intensive counseling plus pharmacotherapy. For each category the average 12-months continuous abstinence rate and intervention costs were estimated. A dynamic population model for COPD was used to project the long-term (cost-)effectiveness of one year implementation of minimal counseling, intensive counseling and intensive counseling plus pharmacotherapy for 50% of the smoking COPD patients compared to usual care. Time horizon was 25 years. Uncertainty and one-way sensitivity analyses were performed for variations in (the calculation of) the abstinence rates, the type of projection, intervention costs and discount rates. RESULTS: Nine studies were selected. The average 12 months continuous abstinence rates were estimated to be 1.4% for usual care, 2.6% for minimal counseling, 6.0% for intensive counseling and 12.3% for pharmacotherapy. Compared to usual care, the costs per QALY gained for minimal counseling, intensive counseling and intensive counseling plus pharmacotherapy were €16,900, €8,200 and €2,400, respectively. Results were most sensitive to variations in abstinence rates and discount rates. CONCLUSIONS: Compared to usual care intensive counseling and pharmacotherapy resulted in low costs per QALY gained with ratios comparable to results presented for smoking cessation in the general population. Compared to intensive counseling alone, intensive counseling plus pharmacotherapy was cost saving and dominated the other interventions.