OBJECTIVES:In Japan every year, approximately 7000 women are diagnosed with cervical cancer and 2500 die from the disease. The incidence of cervical cancer in women aged 20 to 40 years old is higher than other generations. We estimated the clinical and economic impact of implementing cervical cancer vaccination in Japan, focusing on morbidity and mortality and cost effectiveness from the health care payer’s perspective. METHODS: A Markov cohort model with 12 health states was used. Transition probabilities and utility values were obtained from literature and epidemiologic data from public databases. Direct costs for treatment and screening were estimated from Japanese medical fee schedule. Under the base-case: vaccine coverage was assumed to be 100%; with regular and irregular screening at 13.8% and 40.0% respectively; vaccine efficacy against HPV-16/18 was 95% with overall 27% cross-protection against non-vaccine oncogenic HPV types. Costs and effectiveness were discounted at 1% based on recent economic growth rate in Japan. Sensitivity analyses were undertaken to examine the main variables affecting cost effectiveness. RESULTS: Observed age-specific annual cervical cancer incidence rates and deaths were closely replicated by the model. Vaccinating 12 year old girls was predicted by the model to reduce the number of cases and deaths from cervical cancer by 73%. The cost-effectiveness result of cervical cancer vaccination versus no vaccination was JPY 296,829 per QALY gained. Results were most sensitive to the price of the vaccine, HPV-type distribution, and discount rates. With a discount rate of 3% the incremental cost per QALY gained increased to JPY 1,817,607, still much lower than a recommended threshold value of approximately JPY 6 million per QALY gained. CONCLUSIONS: Prophylactic cervical cancer vaccination of Japanese 12-year old girls is predicted to be a very cost effective way to reduce cervical cancer morbidity and mortality compared with the current situation.