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Purpose: To comparatively evaluate the results of a 2-dose human papillomavirus (HPV) vaccination programme with the AS04-adjuvanted HPV16/18 vaccine (AS04-HPV-16/18v) or HPV-6/11/16/18 vaccine (4vHPVv), in addition to cervical cancer (CC) screening, in Malaysia. Methods: A lifetime Markov model replicating the natural history of HPV in 13-year-old girls was adapted to Malaysia to assess the impact of vaccination on pre-cancerous lesions, genital warts and CC cases, CC deaths, quality-adjusted life years (QALYs), and costs from the perspective of the Malaysian Ministry of Health. Vaccine effectiveness was based on efficacy and HPV type distribution. Both vaccines were assumed to have equal efficacy against vaccine-type HPV but differed for protection against non-vaccine types. Vaccine price parity was used and health and cost outcomes were discounted at 3%/annum. Sensitivity analyses tested the robustness of the results. Results: The model predicted that AS04-HPV-16/18v would result in 361 fewer CC cases and 115 fewer CC deaths than 4vHPVv, whereas 4vHPVv averted 4,241 cases of genital warts over the cohort’s lifetime. Discounted total costs showed savings of 18.50 million Malaysian Ringgits and 246 QALYs in favour of AS04-HPV-16/18v. In one-way sensitivity analyses, the discount rate was the most influential variable for costs and QALYs, but AS04-HPV- 16/18v remained dominant throughout. A two-way sensitivity analysis to assess the longevity of cross-protection for both vaccines confirmed the base-case. Conclusions: In Malaysia, the use of AS04-HPV-16/18v, in addition to screening, was modelled to be dominant over 4vHPVv, with greater estimated CC benefits and lower costs.