OBJECTIVES: In the UK, smoking cessation prescriptions (SCPs) include bupropion, nicotine replacement therapy (NRT) and varenicline, where NRT and bupropion were available around 2000 and varenicline in 2006, with NRT being relatively less expensive. This study evaluates the trends in SCP expenditure from the national payer perspective.   METHODS: From patients >18 years, annual SCPs were obtained between January 1, 2000 - December 31, 2009 from The Health Improvement Network (THIN) database, which holds anonymised longitudinal UK primary care data from >500 practices. Drug prices came from the British National Formulary March 2010 to estimate real growth in expenditure. Expenditure trends were disaggregated by prescription frequency; treatment prevalence, defined as the number of patients receiving a SCP in THIN; SCPs per patient treated; and average drug expenditure per SCP. Sensitivity of 5% was applied towards expenditure.  RESULTS: Total number of SCPs was 9,706 in 2000 and estimated 131,466 in 2009. SCP expenditure were estimated at 7,416,741£ (range:7,045,904-£;7,787,578£) in 2000 (2010 £ values) and 77,904,026£ in 2009 (range:74,008,825-£; 81,799,228£) reflecting a 950.4% real rate of increase. Bupropion prescription frequency was 70.8% in 2000 decreasing to 2.2% in 2009, NRT frequency was 29.2% in 2000 peaking at 94.4% in 2006 and declining to 65.1% in 2009, and varenicline frequency was 16.8% in 2007 increasing to 32.8% in 2009. Treatment prevalence rose from 0.3% in 2000 to 2.0% in 2009, while the average annual SCPs per patient treated increased from 1.5 to 3.0. The average SCP expenditure per SCP decreased to 22.2£ in 2006, however increased to 25.8£ in 2009.  CONCLUSIONS: The expenditure increase reflects increase in treatment prevalence and average annual SCPs per patient treated. Furthermore, the introduction of varenicline may have impacted recent expenditures as the average SCP expenditure per SCP increased at varenicline introduction, suggesting a product shift towards more expensive SCPs.