Aims: The study aimed to assess the budgetary impact (BI) of reimbursing varenicline in patients with chronic obstructive pulmonary disease (COPD), type-2 diabetes mellitus (t2DM) or cardiovascular diseases (CVD). Methods: The BI was estimated comparing the current non-reimbursed scenario versus a projected reimbursed scenario using the Spanish National Health System (SNHS) perspective. A hybrid model was developed using epidemiological data and Markov chains to estimate smoking cessation rates with varenicline during a 5-year horizon. Costs of cessation were considered in the reimbursement scenario only. Efficacy, expressed as a 1-year continuous abstinence rate, was derived from clinical trials. Cost savings due to smoking cessation were extracted from local cost-of-illness studies. Results are shown as incremental cost savings. Univariate sensitivity analysis was also applied. Results: A total of 68,684 patients stopped smoking in the reimbursed scenario compared with 15,208 without reimbursement. In the reimbursed scenario, total savings accounted for (sic) 36.3 million, showing 14.6 million accumulated additional savings compared with the scenario without reimbursement. Sensitivity analyses showed results to be robust with monetary savings starting in the third year of modeling. Conclusion: Reimbursement of varenicline in smoking cessation is a cost-effective health policy in the SNHS in COPD, t2-DM or CVD, and could produce cost savings starting in the third year of implementation. (C) 2016 S. Karger AG, Basel