OBJECTIVES: The burden of pneumococcal disease in adults is substantial, both from the social and economic point of view. This study assessed the cost-effectiveness of the 13-valent pneumococcal conjugate vaccine (PCV13) for the prevention of invasive pneumococcal disease and pneumococcal pneumonia in adults, versus “no vaccination” and versus vaccination with the 23-valent pneumococcal polysaccharide vaccine (PPSV23). METHODS:  A Markov model simulates three different scenarios: no immunization, complete immunization with PPSV23 and with PCV13. The comparison between scenarios allows the estimation of clinical and economic outcomes among which cost-effectiveness (ICER) and cost-utility ratios (ICUR). The model takes into consideration age, risk profile, vaccination status, type of immunization and time since vaccination. Societal perspective was adopted and lifetime horizon was considered. Different sources of data and assumptions were used to calibrate PPSV23 and PCV13 effectiveness. Inpatients resource use was based on 2013 diagnostic-related-group database and experts’ opinion, while national legislation was the main source for unitary costs. RESULTS:  PCV13 shows ICURs of €17,746/QALY and €13,146/QALY versus “no vaccination” and PPSV23, respectively. These results proved to be robust in univariate sensitivity analyses, where all ratios were below the €20,000 threshold, with the exception of the scenario with PCV13 effectiveness halved. In probabilistic sensitivity analysis, 94% of simulations showed cost-effectiveness ratios lower than €20,000/QALY in both scenarios.   CONCLUSIONS: PCV13 compared with “no vaccination” and PPSV23, is a cost-effective strategy in adults in Portugal.