•Introducing a domestic pneumococcal conjugate vaccine is likely to be cost-effective in Cuba.•In a ‘worst case’ scenario, cost per DALY averted was still less than 0.4 GDP per capita.•The impact of the vaccine would need to be monitored following its introduction. To evaluate the cost-effectiveness of introducing a domestic pneumococcal conjugate vaccine (PCV7-TT) into the Cuban National Immunization Program (NIP). We compared PCV7-TT given at two, four and six months of age to a scenario without PCV7-TT, over a ten-year period (2020–2029). We calculated the cost (Cuban pesos – CUP) per Disability Adjusted Life Year (DALY) averted from a Government perspective. We compared results from a static cohort model and a parsimonious prediction model informed by the serotype distribution among pneumococcal carriers and cases. We ran probabilistic and deterministic uncertainty analyses. PCV7-TT could prevent 6897 (95% uncertainty interval, 4344–8750) hospitalizations and 189 (115–253) deaths in children <5 years of age, over the period 2020–2029. This could cost around 25 million (20–31) discounted CUP but would be offset by treatment cost savings of around 23 million (14–31). A parsimonious model predicted less favourable impact and cost-effectiveness but the cost per DALY averted was still less than 0.4 times the current GDP per capita. PCV7-TT is likely to be cost-effective in Cuba. The impact of the vaccine would need to be carefully monitored following its introduction into the NIP.