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A decision-analysis model was developed to evaluate health and economic effects of varenicline compared with other smoking-cessation aids for private health plans, Medicaid plans, or employee populations. Use of varenicline is projected to increase the number of successful smoking cessations after 10 years by approximately 14% compared with bupropion, 25% compared with nicotine patches, and 38% when compared with no pharmacologic aids. Varenicline use also results in immediate health care cost savings, compared with use of bupropion and savings within two years compared with nicotine patches or no aids. Comparing varenicline with no aids, the cost effectiveness of varenicline at two years ranged from $648 per additional cessation in the private health plan model to $836 per additional cessation in the Medicaid model. Employers often experience additional savings from decreased absenteeism and increased productivity, with combined savings in health care plus workplace costs associated with varenicline use of $165 to $457 per smoker over two years