OBJECTIVES: HPV vaccination is recommended in Germany for adolescent girls. The objective of this research was to estimate for Germany, the cost-effectiveness of a candidate prophylactic cervical cancer vaccine with potential cross-protection benefits. METHODS: A Markov model based upon the natural history of HPV and cervical cancer was developed to simulate transitions between health states: Normal, HPV, Cervical Intraepithelial Neoplasia (CIN), Cervical Cancer (CC) stages 1 to 4, and death. Using a lifetime simulation of 12-year old girls, the model was adapted for country-specific epidemiological data: age-specific HPV prevalence, HPV type distribution in cervical disease, prevalence of pre-cancerous lesions, and age-specific CC incidence and mortality. Country-specific screening practices and costs were used with a discount rate of 4% on costs, 1.5% on outcomes. Published efficacy rates were used for the candidate vaccine including a potential cross-protection benefit (i.e., additional efficacy against oncogenic HPV types 31 and 45). Sensitivity analyses were performed on costs, discount rates, efficacies, cross-protection, and age at vaccination. RESULTS: Reductions in CC and related deaths were predicted to be 81% (80% mortality) following vaccination of 12 year old girls. The corresponding cost per life-year gained ranged from €19,600 to €20,700 respectively, depending upon whether the analysis was conducted from a societal or health-care payer perspective. When considering quality of life benefits, the vaccine showed a cost per quality-adjusted life-year of €14,700 (societal) to €15,500 (payer). Results were most sensitive to assumptions about discount rates and age at vaccination. For cohorts of 18, and 25-year-old women, vaccination has estimated cost per QALYs of €16,100 and €18,800 (societal), and €15,300 and €18,000 (payer), respectively. CONCLUSION: Prophylactic vaccination against CC with a candidate HPV 16/18 vaccine is a cost-effective method of reducing precancerous cervical lesions, cervical cancer incidence and mortality in Germany.