OBJECTIVES: A vaccine to prevent infection with human papillomavirus (HPV) types 6, 11, 16 and 18 may soon become available. The current strategy to prevent cervical cancer in the UK is screening every 3 years, beginning at age 25 and then every 5 years for women aged 50+. The current screening coverage rate is 81.2%. The objectives are to assess the health and economic impact of HPV vaccination in association with current screening in the UK compared to screening alone. METHODS: A Markov model of the natural history of HPV infection incorporating screening and vaccination was developed for the UK. A vaccine that would prevent 90% of HPV 6, 11, 16 and 18-associated disease, with 20 years duration and 87% coverage, given to girls at age 12 in conjunction with current screening was compared to screening alone using cost per life-year (LY) and quality-adjusted life-year (QALY). Sensitivity analyses included varying the vaccination cost from £165 to £220 and assuming a lifetime duration for vaccine efficacy. RESULTS: The model predicts the reduction in lifetime risk of cervical cancer attributable to screening in line with already published UK data. Introduction of vaccination, and maintaining the screening programme unchanged, would be expected to reduce the lifetime risk to 0.66%. Vaccination with current screening is associated with an incremental cost-effectiveness ratio (ICER) that varies from £16,000/QALY (£20,600/LY) to £22,000/QALY (£28,200/LY) compared to screening alone, when the vaccination cost is varied from £165 to £220. If a lifetime duration of vaccine efficacy is assumed, the ranges for the ICERs decrease to £12,750/QALY (£16,250/LY) and £17,570/QALY (£22,400/LY) respectively. CONCLUSION: These analyses suggest that adding a quadrivalent HPV vaccine to current screening in the UK may be a cost-effective method for further reducing the burden of cervical cancer.