OBJECTIVES: The aim of this study is to estimate the cost-effectiveness of cervical cancer primary screening with HPV PCR tests in Brazil. METHODS: A Markov model captured the outcomes of 1,000 non-hysterectomized women ages 25 years and older who transitioned annually across possible health states and were screened over a 45-year period in Brazil. This model was used to compare three strategies: (1) cytology alone (2) Pooled HPV with reflex cytology (3) HPV with 16/18 genotyping and reflex cytology, from a payer’s perspective. The one-way and probabilistic sensitivity analyses were performed. Additionally, the screening and cancer treatment costs were calculated according to DATASUS 2012 (Departamento de Informática do Sistema Único de Saúde - Brazil) public data, in Brazilian Real (BRL) and discounted at an annual rate of 5%. RESULTS: The primary screening with the strategy (3) HPV with 16/18 genotyping and reflex cytology, results in earlier detection of clinically relevant high-grade CIN (Cervical Intraepithelial Neoplasia) at the initial visit along with efficient use of healthcare resource in Brazil. In addition, the model suggested an Incremental Cost Utility Ratio (ICUR) and Incremental Cost Effectiveness Ratio (ICER) of 13,266 R$/QALY and 51,389 R$/LYG, respectively, comparing the strategies (3) to (1), whereas, the strategy (2) was dominated by strategy (3). CONCLUSIONS: The current analysis indicated that the HPV with 16/18 genotyping test (strategy 3) is cost-effective for primary cervical cancer screening in women aged ≥25 years in Brazil due to the ICER ≤ 3 Brazilian GDP per capita, according to the World Health Organization’s recommendations.