OBJECTIVES: To understand the disease burden of pneumococcal disease (PD), a major cause of childhood morbidity and mortality in Argentina, and to draw a baseline against which the need for and effectiveness of vaccination with pneumococcal conjugate vaccines might be measured. METHODS: A Markov model was constructed to estimate incidence and mortality rates of PD-meningitis (MEN), bacteremia/septicemia (BACT), pneumonia (PNEU), acute otitis media (AOM)-among a hypothetical, birth cohort of 750 000 Argentine infants born in 2006-2015. A systematic review of the literature was performed to select and incorporate input parameters. Life years and costs in 2006 US$ were expressed as both undiscounted and discounted. RESULTS: The number of PD episodes estimated to occur over a 10-year period in the hypothetical birth cohort were: MEN, 225; BACT, 2 841; PNEU, 2 628; and AOM, 2 066 719. Chronic sequelae of MEN could be expected to cause neurological damage in 43 children and severe hearing issues in 28. Results indicate that there would be 78 PD-related deaths in the cohort (29% due to MEN; 54%, BACT; and 17%, PNEU). The undiscounted life-expectancy for individuals in the birth cohort was estimated to be 72.4 years (29.0 years discounted). Mean, undiscounted, lifetime costs attributed to PD for each child of the cohort totaled US$ 167 (US$ 151 discounted), imposing a total, cohort cost-burden of more than US$ 126 million (US$ 113 million discounted). CONCLUSIONS: The study shows that PD imposes a significant health and economic burden on the Argentine population. This information is essential for assessing the potential health and economic impact of introducing pneumococcal conjugate vaccine into the national immunization schedule.