Varenicline at standard dose is effective for the treatment of tobacco dependence. But, in real post-marketing use, most patients do not receive 12 weeks of varenicline treatment as recommended in the Champix product information. In this study, we evaluated the clinical characteristics of smokers who had received varenicline prescription order and the relationship between the duration of varenicline usage versus the success rate of 6 months abstinence in a health promotion center based smoking cessation clinic. Methods: We reviewed the clinical records of 78 smokers who received varenicline prescription (range: 1-27 weeks) along with practical individual counseling to quit smoking after routine physical examinations from September 2007 to December 2009 at the Health Promotion Center of Samsung Medical Center. Results: All of the smokers were male. Most of them (83.6%) had college or higher education, and 85.2% had high monthly income over $4000. Median age of initiation of smoking was 20 years, 64% started smoking at 20 years, and 61.5% smoked ≤20 cigarettes per day. Of those 78 smokers, 28.2% received more than 12 weeks of varenicline treatment as recommended. Varenicline usage less than 4 weeks, between 4 to 7 weeks, and between 8 to 12 weeks were 20.5%, 28.2%, and 23.1%, respectively. At 6-months, overall 47.4% of smokers continuously abstained from smoking. Of those who completed varenicline treatment more than 12 weeks, 63.6% achieved 6-month continuous abstinence compared with 41.1% who discontinued prematurely. As the duration of varenicline usage elongated by one week, the odds of abstinence increased 1.123 (95% confidence interval [CI] 1.03 to 1.22). Side effects were reported in 32.1% of smokers but no serious adverse events were noticed. Conclusion: Varenicline increased the odds of successful 6-month smoking cessation as the duration of varenicline usage enlongated. Encouraging persistence of varenicline usage may increase the chances of successful long-term smoking cessation. There is a need for further studies to evaluate the reasons for premature discontinuation of varenicline and for the efficacy of treatment extended beyond 12 weeks.