OBJECTIVES: To simulate the potential benefits of implementing infant vaccination with the 10-valent pneumococcal & non-typeable Haemophilus influenzae (NTHi)-protein D conjugate vaccine (PHiD-CV) or the 13-valent pneumococcal conjugate vaccine (PCV13) in Latin American countries. METHODS: Vaccine impact was assessed using a Markov cohort model for Mexico, Brazil, Chile, and Colombia. The model simulates the burden of pneumococcal- and NTHi-related diseases (Invasive Disease (ID), Community Acquired Pneumonia (CAP) and Acute Otitis Media (AOM)) in a birth cohort followed over a lifetime. Epidemiology, disease management and costs are country-specific. Vaccination schemes (3+1) at 90% coverage & price parity were compared to no intervention. Future QALYs and costs discounted at 3.5%, using the health care payer perspective are presented. RESULTS: Mortality impact on ID and CAP for the two vaccines is projected to be comparable under base case conditions which include minimum assumptions of NTHi infection rates. Vaccines are predicted to reduce 12.8 to 39.0 deaths (PCV13) and 12.4 to 37.3 deaths (PHiD-CV) per 100,000 vaccinated children. The model predicts that PHiD-CV will prevent 93 to 494 additional Myringotomies and 651 to 8,314 additional AOM cases per 100,000 vaccinated children, when compared with PCV13. Medical costs averted are estimated similar for ID and CAP. The model predicts that PHiD-CV will prevent 48 to 116% more AOM associated costs to the health care system over lifetime than PCV13. In the scenarios analyzed, both vaccines are cost effective but PHiD-CV generates more QALYs gains (range 0.04%-14.5%) and is cost saving (range 1.88-12.54%) compared to PCV13. CONCLUSIONS: The model shows both vaccines would significantly reduce the clinical & economic burden of Pneumococcal disease and are cost effective for Latin American countries. Nevertheless, due to its greater impact on AOM-related cases and costs, PHiD-CV would generate more QALY gains and is cost-saving to the healthcare system compared to PCV13.