Objective To assess the costs and benefits of two algorithms for cervical cancer screening in Belgium (1) high-risk human papillomavirus (HR-HPV) primary screening and (2) HR-HPV and liquid-based cytology (LBC) co-testing. Methods A decision tree was adapted from published work and parameterised using HORIZON study data and Belgian cost and population data. The theoretical model represents two different screening algorithms for a cohort of 577 846 women aged 25–64 attending routine cervical screening. Scenario analyses were used to explore the impact of including vaccinated women and alternative pricing approaches. Uncertainty analyses were conducted. Results The cost per woman screened was €113.50 for HR-HPV primary screening and €101.70 for co-testing, representing a total cost of €65 588 573 and €58 775 083, respectively, for the cohort; a 10% difference. For one screening cycle, compared to HR-HPV primary, co-testing resulted in 13 173 more colposcopies, 67 731 more HR-HPV tests and 477 020 more LBC tests. Co-testing identified 2351 more CIN2+ cases per year (27% more than HR-HPV primary) and 1602 more CIN3+ cases (24% more than HR-HPV primary) than HR-HPV primary. Conclusion In Belgium, a co-testing algorithm could increase cervical pre-cancer detection rates compared to HR-HPV primary. Co-testing would cost less than HR-HPV primary if the cost of the HPV test and LBC were cost-neutral compared to the current cost of LBC screening but would cost more if the cost per HPV test and LBC were the same in both co-testing and HR-HPV primary strategies.