Background: A recently developed 10-valent pneumococcal non-typable H influenzae protein D-conjugate vaccine (PHiD-CV) is expected to afford protection against more than two thirds of isolates causing IPD in children in Latin America, and also against acute otitis media caused by both Spn and NTHi. OBJECTIVES: to assess the cost-effectiveness of PHiD-CV in comparison to non-vaccination in children under 10 years of age in Argentina, Brazil, Chile, Colombia, Mexico and Peru.  METHODS: We used a static, deterministic, compartmental simulation model. The dosing regimen considered included three vaccine doses (at 2 months, 4 months and 6 months) and a booster dose (at 13 months) (3 + 1 schedule). Model outcomes included number of cases prevented, deaths averted, quality-adjusted life- years (QALYs) gained and costs avoided. RESULTS: The largest effect in case prevention was observed in pneumococcal meningitis (range 26% for Peru up to 47% for Colombia), neurologic sequelae after meningitis (range between 37% for Peru and 65% for Brazil) and bacteremia (range 42% for Argentina up to 49% for Colombia). The model showed a significant proportion of deaths averted annually (range between 17% for Peru and 33% for Brazil). Overall, the health benefits achieved with PHiD-CV vaccination resulted in a gain of QALYs (range 14% for Peru up to 26% for Brazil). Compared to non-vaccination cost-effectiveness analysis demonstrated significant health benefits in favor of 10-valent pneumococcal vaccination implementation, with ICER values between -230 (Chile) and 7,088 (Brazil), $US dollars 2010 per QALY gained. In Chile, negative ICER value reflected net cost savings. Indirect costs affected results more than herd immunity. CONCLUSIONS: the incorporation of the 10-valent pneumococcal conjugate vaccine into routine infant immunization programs in Latin American countries could be a valid a strategy to optimize use of available resources improving both health and quality of life for populations in the region.