The purpose of the study was to analyze drug compliance and efficacy of tilorone in preventing acute exacerbations and improving quality of life (QoL) in patients with moderate to severe COPD and a history of frequent acute respiratory viral infections (ARVI). Materials and methods. The study involved patients with moderate to severe COPD (n = 94; 35 females, 59 males; mean age, 61.8 ± 0.7 years). A comprehensive examination of patients included drug compliance assessment with a specially developed scale, clinical and laboratory parameters measured at inclusion and in 12 months. Twenty three patients with high compliance were treated with tilorone. A control group consisted of low-compliant patients who did not give a consent to take tilorone (n = 20). Results. The significant 1.95-fold reduction in ARVI episodes incidence within 12 months was registered in the tilorone group that resulted in reduction in COPD exacerbation and hospitalizations rates, improvement in physical component of QoL and decrease in a cost of the therapy by 84%. Conclusion. Six-week therapy with tilorone 125 mg once a week, two courses annually, aimed at prevention ARVI in patients with moderate to severe COPD and a previous history of frequent ARVI could significantly reduce a rate of ARVI episodes followed by reduction in the rate of acute exacerbations of COPD, hospitalizations due to COPD and in improvement in physical component of QoL. Tilorone did not change lung function and physical tolerance of COPD patients.