OBJECTIVES: Streptococcus pneumoniae causes significant morbidity and mortality worldwide in both children and adults. The aim of this analysis is to evaluate the cost-effectiveness of vaccinating the Colombia population over 50 years with 13-valent pneumococcal conjugated vaccine (PCV 13) vs. 23-valent pneumococcal polysaccharide vaccine (PPSV23) to estimate the clinical benefits and associated costs from the third-party payer perspective in Colombia. METHODS: A Markov model simulating vaccination and outcomes was adapted to Colombian settings, using a time horizon of 5 years (5% annual discount rate). Comparators were PCV13, PPSV23 (70% coverage) and no vaccination; revaccination with PPSV23 after 5 years in adults at high risk according to CDC criteria was considered. Probabilities and costs were extracted from a literature review, the incidence of diseases was retrieved from local database and costs are presented in 2011 US$. Effectiveness measures were the number of pneumococcal diseases and deaths prevented, as well as life years (LY) saved. Probabilistic sensitivity analyses were developed. RESULTS: Over a 5 year period, vaccinating with PCV13 compared to PPSV23 and no vaccination prevents 3,277 and 15,930 cases of invasive pneumococcal disease; 156,722 and 157,893 cases of hospitalized pneumonia; 11,383 and 12,358 non-complicated pneumonia and 6,613 and 7,691 deaths respectively, PCV13 saves 13,347 LY’s compared to PPSV23 and 18,321 LY’s compared to no vaccination. Total expected savings (considering vaccination costs + medical costs and expressed in US$ millions) for PCV13 was US$ 113.7M compared to PPSV23 and US$ 74.9M compared to no vaccination (total expected costs: US$ 1,462.5M; US$ 1,576.2M and US$ 1,537.4M respectively). CONCLUSIONS: Vaccinating adults over 50 years with PCV13 in Colombia is a cost-saving alternative in comparison to PPSV23 and to no vaccination (US$ 13 and US$9 per patient, respectively). These savings could positive impact the burden of disease and study findings could support the decision-making process in favor of PCV13.