Introduction: Varenicline has recently been added to the market as a new drug for smoking cessation. The aim of the current study was to assess whether varenicline substituted for, or added to, the use of other smoking cessation medications. Methods: We used data from 2,595 smokers taking part in monthly household surveys of representative samples of the English population. We analyzed the percentage of smokers attempting to quit in the past 3 months and using nicotine replacement therapy over the counter (NRT OTC), NRT on prescription (NRT Rx), bupropion, or varenicline from November 2006 to December 2009. This survey covered 3 periods: (a) after the launch of varenicline but before the publication of the National Institute of Health and Clinical Excellence guidance on varenicline in July 2007, (b) the first year following the guidance, and (c) more than 1 year after the guidance. Results: Varenicline usage was negligible in the first period, increased steadily during the second period, and increased less rapidly in the third period to 5.3% of those making a quit attempt (p <.001 for the trend). The percentage of quit attempters using any smoking cessation medication increased nonsignificantly by 2.8 percentage points from 41.7% to 44.5% (p = .268). The use of NRT OTC decreased significantly by 6.2 percentage points from 35.2% to 29.0% (p = .029), whereas the use of NRT Rx increased significantly by 3.7 percentage points from 6.8% to 10.5% (p = .025), and use of bupropion remained unchanged. Conclusions: Increased use of varenicline in England following guidance from the National Institute for Clinical Excellence in 2007 did not appear to substitute for use of other prescription smoking cessation medication. An observed decline in NRT OTC is likely to have been due to other factors.