OBJECTIVE: In Latin America and the Caribbean, routine vaccination of infants against Streptococcus pneumoniae would need substantial investment by governments and donor organizations. Policymakers need information about the projected health benefits, costs, and cost-effectiveness of vaccination when considering these investments. Our aim was to incorporate vaccine, demographic, epidemiologic, and cost data into an economic analysis of pneumococcal vaccination of infants in Latin America and the Caribbean. METHODS: We previously used a structured literature review to develop regional estimates of the incidence of disease. Cost data were collected from physician interviews and public fee schedules. We then constructed a decision analytic model to compare pneumococcal conjugate vaccination of infants with no vaccination across this region, examining only vaccine's direct effects on children. RESULTS: Pneumococcal vaccination at the rate of diphtheria-tetanus-pertussis vaccine coverage was projected to prevent 9 500 deaths per year in children aged 0 to 5 years in the region, or approximately one life saved per 1 100 infants vaccinated. These saved lives as well as averted cases of deafness, motor deficit, and seizure result in 321 000 disability-adjusted life years (DALYs) being averted annually. At vaccine prices between US$5 and US$53 per dose, the cost per DALY averted from a societal perspective would range from US$154 to US$5 252. CONCLUSION: Pneumococcal conjugate vaccine was highly cost-effective up to $40 per dose. Introduction of pneumococcal vaccine in the Latin American and Caribbean region is projected to reduce childhood mortality and to be highly cost-effective across a range of possible costs.