There is a large difference in the prevalence of cervical cancer between European countries. Between European Union countries, cervical cancer is the most prevalent in Lithuania. Currently we have available vaccines for different types of human papillomavirus virus (HPV), but we lack evidence on how the vaccination would be cost-effective in low-resource Eastern European countries like Lithuania. To create a simulation model for the Lithuanian population; to estimate epidemiological benefits and cost-effectiveness for a HPV16/18 vaccination programme in Lithuania. For the cost-effectiveness analysis, we used Lithuanian population mathematical simulation and epidemiological data modelling. We performed comparative analysis of annual vaccination programmes of 12-year-old or 15-year-old girls at different vaccine penetration levels. Lithuanian female population at all age groups. A vaccination programme in Lithuania would gain an average of 35.6 life years per death avoided. Vaccinated girls would experience up to 76.9% overall reduction in incidence of cervical cancers, 80.8% reduction in morbidity and 77.9% reduction in mortality over their lifetime. Cost per life year gained with different vaccine penetration levels would range from 2167.41 Euros to 2999.74 Euros. HPV vaccination in Lithuania would have a very positive impact on the epidemiological situation and it would be cost-effective at all ranges of vaccine penetration. Vaccination in Lithuania in the long term potentially could be more cost-effective due to avoiding early disease onset and lower accumulation of period costs.