In the United States, uptake of the pneumococcal polysaccharide vaccine (PPSV23) among high-risk individuals aged 65 years is persistently low, and more needs to be done. The intricacy of the adult immunisation schedule is one obstacle to increased vaccine coverage. The cost-effectiveness of methods to promote pneumococcal vaccination uptake in high-risk individuals aged 50–64 years was compared in this exploratory study. A Markov model was used to compare methods for non-immunocompromised 50–64-year-olds: 1) existing pneumococcal polysaccharide vaccination guidelines; 2) current recommendations supplemented with an intervention; 3) PPSV23 with pneumococcal conjugate vaccine (PCV13) for high-risk patients with no intervention; or 4) both vaccinations with no intervention for all 50-year-olds. In sensitivity studies, parameters such as CDC data and other US data were changed widely. Vaccinating high-risk people with PPSV23/PCV13 was the least expensive approach in the study, with total expenditures of $424/person. Vaccinating all people over the age of 50 with PPSV23/PCV13 cost $40 extra but added 0.00068 quality-adjusted life years (QALY), or $57,786/QALY gained. 

In multi-way sensitivity analyses, the current recommendations/intervention programme strategy was chosen at a $100,000/QALY threshold only if the rate of non-bacteremic pneumococcal pneumonia or PCV13 serotype coverage was much lower than the base case values. As a result, in most scenarios, an intervention programme to increase pneumococcal vaccination uptake among high-risk 50–64 year-olds was not cost-effective. Vaccination high-risk persons with both PCV13 and PPSV23 may be cost-effective, and vaccinating all 50-year-olds with both vaccines may be explored.