OBJECTIVES: This study estimated health impact and cost-effectiveness of adding a quadrivalent HPV vaccination program for preadolescent girls to the existing cervical cancer screening program from the Thai payer perspective. METHODS: A published transmission-dynamic model was adapted to Thailand setting. Both direct and indirect (herd immunity) benefits were captured by the model. Model inputs were obtained from literature, unpublished data and expert opinion. A proposed tender price of vaccine shown on recent news plus logistics, management and administration costs were used as vaccine-related costs to reflect the real situation of Thailand school-based HPV vaccination. Future costs and outcomes were discounted at 3%. Two vaccination strategies of combining cervical cancer screening with routine vaccination (11- to 12-year-old females) and with routine plus 5-year catch-up vaccination (13- to 24-year-old females) were compared to screening program alone. RESULTS: Adding HPV vaccination to the screening program provided both short- and long-term health benefits. Compared with current screening practice over 100 years, routine vaccination reduced cumulative incidence of cervical cancer (-54%), CIN1 (-71%), CIN2/3 (-70%), genital warts among females (-75%) and males (-63%), and cervical cancer deaths (-52%). Routine vaccination also resulted in reduction of disease costs for cervical cancer (-24%), CIN1 (-42), CIN2/3 (-41%), genital warts in females (-52%) and males (-42%). The reduction in HPV6/11-related disease incidence and costs avoided occurred relatively soon after vaccination, especially CIN1 and genital warts. Considering the recommended threshold of 160,000 THB/QALY, both routine and routine plus catch-up programs are cost-effective with discounted incremental cost-effectiveness ratios (ICER) of 35,124 and 34,426 THB/QALY, respectively. The ICER increased by about 31% for both strategies when HPV6/11-related effects were excluded.  CONCLUSIONS: The school-based HPV vaccination program, using the quadrivalent HPV vaccine, is cost-effective, particularly when catch-up vaccination is incorporated. The results support decision-making process to include HPV vaccination in Thailand NIP.