OBJECTIVES: Patients with chronic obstructive pulmonary disease (COPD) are at risk of pneumococcal infection. A 13-valent pneumococcal-conjugate vaccine (PCV13) has recently been approved for adult protection against S. pneumoniae. This study estimated the clinical and economic consequences of vaccinating COPD patients aged ≥50 years with PCV13 compared to current vaccination recommendations using a 23-valent pneumococcal-polysaccharide vaccine, from the Spanish Healthcare System perspective. METHODS: A microsimulation model with a Markov process accounting for risks and costs for invasive pneumococcal disease (IPD) and all-cause nonbacteremic pneumonia (NBP) was developed. Prevalence, mortality rates, vaccination and serotype coverage, and vaccination and disease-related costs (€2013) were based on published data. Vaccines effectiveness was modified by a waning effect over time. Herd-immunity and revaccination were not considered. Outcomes and costs (both discounted at 3%/year) were simulated 100 times with, 1.6 million COPD patients per simulation. Outcomes were pneumococcal cases averted and incremental cost–effectiveness ratio (ICER) in terms of cost per life-year gained (LYG). Sensitivity analyses were performed modifying the time horizon, discount rate and vaccination coverage. RESULTS: Over a 5-year period, the use of PCV13 vs current vaccination strategy in adult COPD subjects would prevent 529 IPD cases, 6,329 inpatient-NBP cases, and 697 outpatient-NBP cases. Additionally, 231 IPD and 148 inpatient-NBP related deaths would be averted. The ICER was €24,557/LYG for PCV13 vs current vaccination strategy. In sensitivity analyses, ICER ranged from €26,986/LYG (when changing discount rate from 3% to 5%) to €7,661/LYG (when changing vaccination coverage from 80% to 66%). Using a lifetime horizon 1,271 IPD cases, 10,294 inpatient-NBP cases, and 2,072 outpatient-NBP cases would be prevented, with an ICER of €5,030/LYG. CONCLUSIONS: At a willingness-to-pay of €30,000/LYG, PCV13 vaccination in COPD patients aged ≥50 years in Spain is a cost-effective strategy compared to current vaccination recommendations under both 5-year and lifetime time horizons.