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Introduction The SMART Quit Clinic Program (FAHSAI Clinic) has been implemented in Thailand since 2010; however, it remains unclear whether the benefits gained from this program justify its costs. We assessed its cost-effectiveness compared to usual care in a population of Thai smokers with cardiovascular disease (CVD) from a societal perspective. Methods We conducted a cost-utility analysis using a Markov model to simulate lifetime costs and quality-adjusted life years (QALYs) of Thai smokers aged ≥35 years receiving smoking cessation services offered from FAHSAI Clinic or usual care over a horizon of 50 years. The model used a 6-month continuous abstinence rate from a multicenter prospective study of 24 FAHSAI Clinics. A series of sensitivity analyses including probabilistic sensitivity analysis were conducted to assess robustness of study findings. Cost data are presented in US$ for 2020. Results The FAHSAI Clinic was dominant as it was less costly ($9537.92 vs $10964.19) and more effective (6.06 vs 5.96 QALYs) compared with usual care over the 50-year time horizon. Changes in risks of stroke and coronary heart disease among males had the largest impact on the cost-effectiveness findings. The probability that FAHSAI Clinic was cost-effective was 99.8% at a willingness-to- pay threshold of $5120. Conclusions The FAHSAI Clinic smoking cessation program was clinically superior and cost-saving compared to usual care for Thai patients with CVD in all scenarios. A budget impact analysis is needed to estimate the financial impact of adopting this program within the Thai healthcare system.