OBJECTIVES: To develop a Markov model that can be calibrated to different countries; to facilitate country-specific economic evaluations of a vaccine that protects against infection with multiple human papillomavirus (HPV) types. METHODS: We developed an Excel-based Markov model of the natural history of HPV and cervical cancer using a cycle length of six months for transitioning between health states (Normal, HPV, Cervical Intraepithelial Neoplasia (CIN) 1, CIN 2, CIN 3, Cervical Cancer (Stages 1 to 4), and death. Health states are stratified by HPV type (16, 18, 31, 45, 52, Other Oncogenic, and Non-oncogenic). Using a lifetime simulation of 12-year old girls, the model was calibrated to current data for two European countries (Netherlands, United Kingdom (UK)). Calibration endpoints included: 1)Age-specific HPV prevalence; 2)HPV type distribution in cervical disease; 3)Prevalence of pre-cancerous lesions; and 4)Age-specific cervical cancer incidence and mortality. Observed screening practices and coverage (three-yearly for UK, five-yearly for Netherlands) were used for calibrating to a screened environment. Transition probabilities were varied, within established ranges, to reproduce calibration endpoints. RESULTS: Model-predicted outcomes correlated well with observed data for both UK and The Netherlands. Overall, HPV prevalence was comparable for UK (model-predicted= 7.1%; observed =9.6%) and Netherlands (model-predicted =6.4%; observed = 9.2%). Differences between countries were observed in other endpoints, such as crude cervical cancer incidence per 100,000 (UK: model-predicted = 10.4, observed = 10.2; The Netherlands: model-predicted = 8.5, observed = 8.1), as well as cervical cancer mortality per 100,000 (UK: model-predicted = 5.2, observed = 5.1; The Netherlands: model-predicted = 2.8, observed = 2.9). CONCLUSIONS: A model of the natural history of HPV and cervical cancer was successfully calibrated to two countries. It is important to calibrate to several epidemiological endpoints in countries so that health economic benefits of vaccine can be accurately projected in future cost-effectiveness analyses.