Aim. To provide a rationale for choosing the optimal tactics of vaccination against pneumococcal infection in patients with chronic obstructive pulmonary disease (COPD) in the context of evidence-based medicine and on the basis of immunological and clinical data. Subjects and methods. Patients with COPD were examined during a year after vaccination with a 13-valent pneumococcal conjugate (Prevenar-13, PCV13) and a 23-valent pneumococcal polysaccharide (Pnemo-23, PPV23) vaccines. The following vaccination schemes were used: PCV13 monovaccination, PPV23 monovaccination, sequential vaccination with PPV23/PCV13, and sequential vaccination with PCV13/PPV23. Results. Vaccination using all the analyzed schemes in the patients with COPD caused a statistically significant reduction in the frequency of exacerbations, the number of antibiotic cycles, and the number of hospital admissions, as shown by the results of analysis of short-term data. The use of PCV13 was followed by additional effects that were unobserved in the use of PPV23, namely: it promoted the formation of immunological memory to Streptococcus pneumoniae antigens, resulted in the enhanced activity of nonspecific resistance factors, and caused activation of antiviral defense factors. Conclusion. If patients with COPD need to be vaccinated against pneumococcal infection, preference should be given to PCV13 monovaccination. Short-term observations have shown that the sequential use of pneumococcal conjugate and polysaccharide vaccines is redundant and gives no additional benefit to patients with COPD. However, the sequential application of both vaccines may have additional advantages in the long term.