To assess the cost-effectiveness of universal vaccination of 11-year-old girls against human papillomavirus (HPV) infection and increased screening coverage to prevent cervical cancer in Japan where the coverage of Papanicolaou smears is very low. A cost-utility analysis from a societal perspective. Japan, 2010. The female Japanese population aged 11 years or older. A Markov model of the natural history of cervical cancer was constructed to compare six strategies: i.e. a screening coverage rate of 20, 50 and 80% with and without routine vaccination at age 11. Cervical cancer incidence, quality-adjusted life years (QALYs), costs and incremental cost-effectiveness ratios. Expanding the coverage of Papanicolaou smears from the current level of 20-50 and 80% yields a 45.5 and 63.1% reduction in cervical cancer incidence, respectively. Impact of combined strategies increases with coverage. Coverages of 20, 50 and 80% showed a 66.1, 80.9 and 86.8% reduction in disease, respectively. The costs of strategies with vaccination are four times higher than the cost of strategies without vaccination. Vaccinating all 11-year-old girls with bivalent vaccines with a Papanicolaou smear coverage rate of 50% is likely to be the most cost-effective option among the six strategies. The introduction of HPV vaccination in Japan is cost-effective as in other countries. It is more cost-effective to increase the coverage of the Papanicolaou smear along with the universal administration of HPV vaccine.