Objective: Testing for human papillomavirus (HPV) 16 and 18 genotypes, which are known to cause approximately 65-70% of invasive cervical cancer cases, may allow clinicians to identify women at highest risk for underlying cervical intraepithelial neoplasia missed by Pap cytology. Our objective was to determine the cost-effectiveness of adding HPV-16 and 18 genotype triage to current cervical cancer screening strategies in the United States. Methods: We developed a lifetime Markov model to assess the cost-effectiveness of the following cervical cancer screening algorithms: (1) liquid-based cytology (LBC), (2) LBC + HPV triage, (3) HPV + LBC triage, (4) co-screening, (5) co-screening + HPV genotyping, and (6) HPV only + HPV genotyping. Costs were estimated from a payer perspective in 2007 U.S. dollars. Outcome measures included lifetime risk of cervical cancer, quality-adjusted life years saved (QALYs), and incremental cost-effectiveness ratios (ICERs). Results: In our model, the use of HPV genotyping strategies prevented 51-73 deaths per 100,000 women screened compared to screening using LBC followed by HPV triage and 4-26 deaths compared to co-screening with LBC and high-risk HPV. Use of HPV genotyping to triage all high-risk HPV-positive women every three years had an ICER of $34,074 per QALY compared to HPV and LBC co-screening. HPV genotyping with co-screening was the most effective strategy and had an ICER of $33,807 per QALY compared to HPV genotyping for all high-risk HPV-positive women. Conclusion: The addition of HPV-16 and -18 genotype triage to HPV and LBC co-screening was a cost-effective screening strategy in the United States. © 2010 Published by Elsevier Inc.