OBJECTIVES: Two human papillomavirus (HPV) vaccines are available worldwide: a bivalent vaccine (BV) targeting oncogenic high-risk HPV-16/18 and a quadrivalent vaccine (QV) targeting both high-risk HPV-16/18 and low-risk HPV-6/11. Based on data in their respective trials, BV is likely to have higher efficacy against non-vaccine oncogenic HPV types (cross protection). QV has an effect against genital warts (GW). The potential effect of both vaccines in Thailand on cervical intraepithelial neoplasia grade 1-3 (CIN1-3), GW, cervical cancer (CC) and related treatment costs was investigated. METHODS: A static model estimated the above outcomes over a one-year period at steady state versus the current situation. Costs were assessed from a healthcare payer’s perspective. Epidemiological and cost data were obtained from published sources; efficacy figures were based on the latest clinical trial results from each vaccine and region-specific HPV distribution among lesions (local data was used where possible). Sensitivity analyses were conducted on all input data, such as with scenarios where the incidence and costs of treating GW were varied. RESULTS: BV was projected to avert 8,896 cases of CC annually. BV potentially would result in an additional reduction of 5,470 CIN1, 5,177 CIN2/3 and 1,053 CC cases annually compared with QV, while QV potentially would prevent an additional 125,957 GW cases annually. The additional cost saved with BV was estimated at THB 345.6 million annually compared with QV. Sensitivity analyses report additional cost-savings for the BV compared with QV under all scenarios. CONCLUSIONS: The level of cross protection of BV potentially would allow for an additional reduction in CC and HPV related morbidity compared to QV; under our model, this resulted in cost averted that offset the economic benefit QV will have in preventing GW in Thailand.