The cost-effectiveness of smoking cessation interventions is well documented. However, most studies are based on randomized controlled trials (RCTs) and provide little information on the differences between subgroups. This study assessed the relative cost-effectiveness of smoking cessation interventions offered to various subgroups of smokers, based on real-life data. Regression analyses provided information on the factors determining abstinence and costs and led to the formation of relevant subgroups of smokers. Probabilistic Markov modeling was then used to estimate the relative cost-effectiveness of smoking cessation interventions for the entire database population and for the subgroups compared to a no-intervention case. The ICER for the base case population was estimated at 1,358 euro. This is consistent with results from the existing literature. Group simulations showed lower ICERs for men, hospitals, and light smokers and falling ICERs with increasing age. Despite differences in the cost-effectiveness ratios between subgroups our results do not justify any kind of subgroup differentiation in a smoking prevention policy.