Background: The objective of this study was to assess the cost-effectiveness of PPV23, when compared with no vaccination, PCV13 and the sequential use of PCV13 and PPV23 in adults 60 years and older in Colombia. Methods & Materials: A state-transition Markov model was developed. Five health states were considered: no pneumococcal disease, invasive pneumococcal disease (IPD), nonbacteremic pneumococcal pneumonia (NBPP), postmeningitis sequelae (PMS), and death. A cohort of 60-year-olds in Colombia was followed up to 100 years of age or until death. Vaccine efficacy against IPD was obtained from a meta-analysis and a clinical trial. Vaccine efficacy against NBPP was obtained from a population-based cohort study and a clinical trial. Costs were obtained from the Pan American Health Organization, Colombian official list prices and published literature. Costs and outcomes were discounted at 5.0% per year, the analysis took the perspective of the third payer and costs were expressed in Colombia Pesos and inflated to 2016 rates where necessary. Incremental cost-effectiveness ratio (ICER) per quality-adjusted life year (QALY) gained was the main outcome. The World Health Organization definition of less than 3 times of per capita Gross Domestic Product in Colombia (i.e. COP 68,933,306 per QALY gained) was used as the threshold of cost-effectiveness. Sensitivity analyses were conducted to test the robustness of the result. Results: A cohort of 3,324,291 immunocompetent individuals was followed. In the base case analysis, compared to no vaccination, vaccinating with PPV23 was associated with a reduction of cost by COP 28.5 billion and an increase in QALYs by 2,844. Compared to vaccinating with PCV13, vaccinating with PPV23 was associated with a reduction of cost by COP 97.7 billion and an increase in QALYs by 755. The sequential strategy was estimated to have incremental cost of COP 138.2 billion and incremental QALYs gained of 393 compared to PPV23, however it was deemed not cost-effective at an ICER of COP 351,514,729. Conclusion: In conclusion, our study suggests that vaccination with PPV23 is the optimal strategy for prevention of pneumococcal disease in Colombia in adults 60 years and older.