Background: The Belgian Superior Health Council (SHC) recently added a 13-valent pneumococcal conjugate vaccine (PCV13) to its recommendations for adult pneumococcal vaccination. This study addresses the policy question regarding whether a single dose of PCV13 should be reimbursed among Belgian adults aged 65-84 years with chronic comorbidities ("moderate-risk") or immunosuppression ("high-risk")., Methods: A cohort model was developed to project lifetime risks, consequences, and costs of invasive pneumococcal disease (IPD) and pneumococcal community-acquired pneumonia (CAP). Parameter values were estimated using published literature and available databases, and were reviewed by Belgian experts. PCV13 effectiveness was assumed to be durable during the first 5 years following receipt, and to progressively decline thereafter with 15 years protection. The Belgian National Health Insurance perspective was employed., Results: Use of PCV13 (vs. no vaccine) in moderate/high-risk persons aged 65-84 years (n = 861,467; 58% vaccination coverage) would be expected to prevent 527 cases of IPD, 1,744 cases of pneumococcal CAP and 176 pneumococcal-related deaths, and reduce medical care costs by €20.1 million. Vaccination costs, however, would increase by €36.9 million and thus total overall costs would increase by €16.8 million. Cost per QALY gained was €17,126. In probabilistic sensitivity analyses, use of PCV13 was cost-effective in 97% of 1,000 simulations., Conclusions: Reimbursement of PCV13 in moderate/high-risk Belgian adults aged 65-84 years would be cost-effective from the Belgian healthcare perspective., Competing Interests: Funding for this research was provided by Pfizer Inc. to Policy Analysis Inc. (PAI). Mark Atwood and Derek Weycker are employed by PAI; Sophie Marbaix and Annick Mignon are employed by Pfizer NV/SA, and Reiko Sato is employed by Pfizer Inc. Willy E. Peetermans, Jan Verhaegen, and Lieven Annemans have no conflicts of interest for this work. There are no patents, products in development, or marketed products to declare. Authors’ commercial affiliations do not alter our adherence to PLOS ONE policies on sharing data and materials.