Using population and epidemiologic data for 33 countries in Latin America and the Caribbean (LAC), a model-based approach estimated averted cervical cancer cases and deaths, disability-adjusted life years (DALYs) and incremental cost-effectiveness ratios (I$/DALY averted) for human papillomavirus (HPV) vaccination of young adolescent girls. Absolute reduction in lifetime cancer risk varied between countries, depending on incidence, proportion attributable to HPV-16 and 18, and population age-structure; for example, with 70% coverage, cancer reduction ranged from 40% in Mexico to more than 50% in Argentina. Screening of women over age 30 three times per lifetime, after vaccinating them as pre-adolescents, is expected to provide a relative increase of 25% to 30% in mortality reduction. Countries with the highest risk of cancer (age-standardized rate > 33.6) accounted for only 34% of deaths averted with vaccination, highlighting why a regional universal vaccination approach will be most effective in reducing the overall global burden. At I$25 per vaccinated girl ($5 per dose), for all 33 countries, the cost per DALY averted is less than I$400; at I$10 ($2 per dose) the vaccine is cost saving in 26 out of 33 countries. For all countries, ratios become less attractive (i.e., increase) as the cost of the vaccine increases. For example, at current vaccine prices ($120 per dose), the cost per DALY averted is I$7,300 in Mexico, I$3,700 in Nicaragua, and I$6,300 in Costa Rica. Vaccine price has an even greater effect on predicted affordability. For the 33 countries, vaccinating 5 consecutive birth cohorts at 70% coverage would cost $360 million at $5.00 per dose, $811 million at $12.25 per dose, and $1.26 billion at $19.50 per dose. In the LAC region, if effective delivery mechanisms can achieve high coverage rates in young adolescent girls, vaccination against HPV-16 and 18 will provide similar health value for resources invested as other new vaccines such as rotavirus. If the cost per vaccinated girl is less than I$25 HPV-16/18 vaccination would be very cost-effective in all 33 countries; for it to be affordable, costs may need to be lower.