OBJECTIVES Smoking is the leading avoidable cause of premature morbidity and mortality in the United States, attributable to over 400,000 annual deaths and $167 billion in healthcare costs. Nicotine addiction remains a key barrier to smoking cessation; for this reason, repeated intervention and multiple quit attempts are necessary. Stepped care is possibly a viable intensive approach for achieving long-term smoking cessation. This study uses modeling techniques to predict outcomes of a current study of stepped care in smoking cessation. It is expected that, though more costly, incremental cost-effectiveness of stepped care will fall well short of accepted thresholds. METHODS A simulation model was created in TreeAge to replicate the Step Care study. Both arms receive pharmacotherapy and counseling; these therapies intensify in the step care arm. Various data sources were used to estimate transition probabilities and costs. The model was run 1,000 times to produce estimates of cost-effectiveness of the stepped care regimen relative to repeat therapy in producing point-prevalent cessation. RESULTS As expected, the model produced a favorable incremental cost-effectiveness ratio (ICER) for stepped care relative to repeat care ($941/quit). Step care and Recycle arms produced mean costs of $740 (95% CI: $540-840) and $665 (95% CI: $520-740), respectively. On average, 31% of step care patients achieved point-prevalent cessation at study end, compared to only 23% of patients in the recycle. In the simulation, 37% of step care patients required each step of therapy; in the recycle arm, an average 2.2 quit attempts were made with patch therapy. CONCLUSIONS The results of the Step Care simulation are promising for achieving progress in tobacco cessation efforts. The population represented in the Step Care study is a difficult-to-treat population—predominately low-income smokers with high rates of nicotine dependence. Treatment guidelines suggest this population to be appropriate for more intensive intervention.