OBJECTIVES Evaluating the cost-effectiveness and cost-utility of a pharmacological intervention for smoking cessation comparing varenicline, bupropion, nicotine replacement therapy (NRT) and unaided cessation in Colombia. METHODS A full economic evaluation was made using the BENESCO (Benefits of Smoking Cessation on Outcomes) model. Such model simulates a cohort of smokers making a single attempt to quit, using different strategies. The model was inputted demographic and epidemiological data corresponding to the Colombian adult population. A systematic review was made to identify the effectiveness of varenicline and the alternative interventions. This review was complemented by consulting available data sources in Colombia in order to estimate disease burden for lung cancer, chronic obstructive pulmonary disease, coronary hearth disease and stroke. The cost of attending these diseases was estimated from a third-payer perspective using HMO and health care provider records. The medicament's cost corresponded to the average of a survey of prices regarding a set of pharmaceutical vendors representative of the market. It was assumed that unaided cessation involved no cost for the third-payer. The clinical and economic results of the four intervention options were projected using the BENESCO model at 2-, 5-, 10- and 20-year time-horizons; such projections were used to calculate incremental cost-effectiveness (ICER) and cost-utility (ICUR) ratios. Future clinical and economic outcomes were discounted at a 3% annual rate; all costs were assessed in US$2007. RESULTS Varenicline dominated NRT and bupropion considering all time-horizons. When compared to unaided cessation, dominance was found in 20-year and lifetime projections; in 10-year projections it was found an ICUR=USD$11,711 for QALY gained and ICER=USD$24,349 per life year gained; however, varenicline was not cost-effective when evaluating 2-5 year projections. CONCLUSIONS Supportive pharmacological interventions for smoking cessation could be promising alternatives for controlling the diseases being evaluated. Varenicline is the most cost-effective of the interventions currently available in Colombia.