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OBJECTIVES: To estimate the costs, benefits and cost-effectiveness of vaccination for rotavirus gastroenteritis in eight Latin American and Caribbean countries: Argentina, Brazil, Chile, the Dominican Republic, Honduras, Mexico, Panama, and Venezuela. METHODS: An economic model was constructed to estimate the cost-effectiveness of vaccination from the health care system perspective, using national administrative and published epidemiological evidence, country-specific cost estimates, and vaccine efficacy data. The model was applied to the first five years of life for the 2003 birth cohort in each country. The main health outcome was the disability-adjusted life year (DALY), and the main summary measure was the incremental cost per DALY averted. A 3% discount rate was used for all predicted costs and benefits. Sensitivity analyses evaluated the impact of uncertainty regarding key variables on cost-effectiveness estimates. RESULTS: According to the estimates obtained with the economic model, vaccination would prevent more than 65% of the medical visits, deaths, and treatment costs associated with rotavirus gastroenteritis in the eight countries analyzed here. At a cost of US $24 per course (for a two-dose vaccine), the incremental cost-effectiveness ratio ranged from US $269/DALY in Honduras to US $10 656/DALY in Chile. Cost-effectiveness ratios were sensitive to assumptions about vaccine price, mortality, and vaccine efficacy. CONCLUSIONS: Vaccination would effectively reduce the disease burden and health care costs of rotavirus gastroenteritis in the Latin American and Caribbean countries analyzed here. From the health care system perspective, universal vaccination of infants is predicted to be cost-effective, based on current standards.