Objective: To assess the relative cost-effectiveness of a high-intensity treatment (HIT) and a low-intensity treatment (LIT) for smoking cessation. Methods: The societal and health care perspective economic evaluation was based on the reported number of quitters at 12-month follow-up (point prevalence) from a randomized controlled trial of 2 smoking cessation programs in Sweden. Future disease-related costs (in Swedish kronor [SEK] 2004; SEK7.35 = USD1) and health effects (in quality-adjusted life-years [QALYs]) were estimated via a Markov model comprising lung cancer, chronic obstructive pulmonary disease, and cardiovascular disease including stroke with costs and QALYs discounted 3% annually. Results: HIT was more effective than LIT (23% vs. 16% quitters), but at a considerably higher intervention cost: SEK26,100 versus 9,100 per quitter. The model-estimated societal costs avoided did not balance the higher intervention costs, so the incremental cost-effectiveness ratio (ICER) amounted to SEK100,000 per QALY for HIT versus LIT. All sensitivity analyses indicated an ICER below SEK300,000 and that HIT is the preferred option if the decision maker willingness-to-pay exceeds SEK50,000 per QALY. Compared with no intervention, LIT was cost saving, whereas HIT was estimated at SEK8,400 per QALY. Conclusions: Compared with no smoking cessation program, it is a societal waste not to implement the LIT as it is estimated to result in lower societal costs. The incremental cost per QALY gained of SEK100,000 for HIT is considered very cost-effective in Sweden. Thus, if smoking cessation programs are judged in the same manner as other Swedish health care measures, the high-intensity program should be chosen before the low-cost program.