OBJECTIVES: . Smoking is the leading cause of preventable death in El Salvador (50%) and results in many serious comorbidities, including lung cancer, coronary heart disease, stroke and chronic respiratory disease.  The aim of this study was to evaluate the cost-utility of varenicline compared to other existing strategies for smoking cessation within a 5-year time horizon in El Salvador using the healthcare payer’s perspective.  METHODS: . The Benefits of Smoking Cessation on Outcomes (BENESCO) simulation model was used for an adult cohort (n=4,537,803). Diseases included were: stroke, lung cancer, coronary heart disease and chronic obstructive pulmonary disease.  Smoking cessation therapies compared were: varenicline (0.5 – 2 mg/day), bupropion (300 mg/day), nicotine replacement treatment (NRT) (5-10 mg/day) and unaided cessation.  Effectiveness measure was: quality-adjusted life year gained (QALY’s), which was obtained from published literature.  Resource use and costs data were obtained from El Salvador’s Ministry of Health and Social Security official databases (2010). The model used a 3% discount rate for costs (expressed in 2010 US dollars) and QALYs.  Probabilistic sensitivity analyses (PSA) were conducted and acceptability curves were constructed. RESULTS: . Varenicline reduced smoking related morbidity, mortality and healthcare costs. After 5 years, Varenicline gained 306,158 QALYs, which represents 73, 94 and 178 more QALYs than bupropion, NRT and unaided cessation, respectively.  Overall costs showed varenicline as the least expensive option against bupropion (+US$328,558), NRT (+US$412,730) and unaided cessation (+US$777,124).  Cost-effectiveness analyses showed that varenicline was the dominant strategy. Acceptability curves showed that varenicline would be cost-effective within <3 GDP per capita threshold. PSA results support the robustness of the findings. CONCLUSIONS: . Smoking cessation therapy with varenicline is cost-saving in El Salvador. These results could help to reduce the tobacco related disease burden and align cost-containment policies