OBJECTIVES: To evaluate life time cost-effectiveness of all available smoking cessation pharmacotherapies in Australia. METHODS: A Markov model using Monte Carlo simulations was constructed to estimate incremental cost-effectiveness ratios (ICERs) of seven smoking cessation pharmacotherapies (bupropion, varenicline, NRT-patches, NRT-gum, inhalers, lozenges, and nasal spray) compared to no pharmacotherpy. A life time horizon was considered from the perspective of the Australian health care system. Three health states were identified; current smokers, quitters and dead. All model entrants were assumed to be current smokers. The 12 month relative chance of quitting associated with each pharmacotherapy was determined based on a systematic literature review of available clinical evidence. Tobacco-related mortality rates for 11 diseases were included while tobacco-related morbidity rates were excluded due to insufficient evidence. Relapse rates for the first five years after quitting were also included. The difference in tobacco related fatalities for between current smokers and quitters represented the total mortality benefit associated with each pharmacotherapy. Pharmacotherapy costs and direct mortality related costs were included. Sensitivity analysis in addition to sub-group analysis by age and gender was also conducted and results were expressed in terms of cost per life years (LY) gained. RESULTS: For male subjects, the ICER estimates varied from $2292/LY gained to $54 037/LY gained while for female subjects the same ranged from $1998/LY gained to $65 302/LY gained. The average ICER estimates were least favourable at age 20, improving in favourability to ages 50–60 and then declining in favourability thereafter. Although the cost-effectiveness estimates varied with age, the trends were consistent across age groups for both genders. Varenicline was the most cost-effective therapy and inhalers were the least cost-effective therapy for smoking cessation among all age groups and both genders. CONCLUSIONS: All smoking cessation pharamcotherapies that were considered in the analysis demonstrated cost-effectiveness when compared with no pharmacotherapy.