OBJECTIVES: Use of PCV13 is recommended to the elderly and the adults with immunocompromising conditions. Additionally, use of PCV13 to immunocompromised adults who also receiving a single dose of 23-Valent Pneumococcal Polysaccharide Vaccine (PPV23) before is also recommended (PPV23-PCV13 sequence vaccination). This study is aimed to predict the potential cost-effectiveness of PPV23-PCV13 sequence vaccination to the elderly and immunocompromised adults in Taiwan. METHODS: Cost-effectiveness analysis from societal perspective was performed using a micro-simulation model. Cost-effectiveness of PPV23-PCV13 sequence vaccination versus PPV23 alone vaccination to a population of 50,000 was predicted on the time horizon of 70 years. Parameters in the model included demographic, epidemiological data, direct medical costs, indirect costs and vaccine efficacy data were derived from published literatures and Taiwan’s National Health Insurance Database. All Results of cost-effectiveness analysis were presented by the incremental cost-effectiveness ratio (ICER) to illustrate the incremental cost (in New Taiwan Dollars, NTD) for one additional life-year (LY) gained. Sensitivity analysis was performed to evaluate the robustness of the results of micro-simulation model. RESULTS: Compared with PPV23 alone vaccination, PPV23-PCV13 sequence vaccination definitely increased vaccination cost but it would reduce total costs including vaccination costs, direct medical costs and indirect costs. Overall, PPV23-PCV13 sequence vaccination was more cost-saving than PPV23 alone vaccination. And, PPV23-PCV13 sequence vaccination would save an additional 0.0065 discounted LYs. The ICER for PPV23-PCV13 sequence vaccination for the elderly and immunocompromised adults was estimated about -284,000 NTDs per LY. CONCLUSIONS: PPV23-PCV13 sequence vaccination could achieve potential health economic and clinical benefits. For the elderly and immunocompromised adults in Taiwan, PPV23-PCV13 sequence vaccination was considered as the dominant vaccination strategy compared with PPV23 alone vaccination.