This study was aimed at investigation of clinical efficacy and safety of high frequency chest wall oscillation (HFCWO) method in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Methods . This was a prospective randomized controlled comparative study. Patients hospitalized for AECOPD (GOLD III or IV stage; mean FEV 1, 37% pred.) were included. In first two days of admission, all patients were randomized to HFCWO treatment (Vest Ò Airway Clearance System; 15–25 min b.i.d.; oscillation frequency, 10–15 Hz; pressure, 4–6 cm H2O) or standard therapy (the control group). Results . Fifty patients completed the study: 25 patients in HFCWO group and 25 patients in the standard therapy group. Therapy with HFCWO was associated with increasing sputum volume to the 3 rd and the 7 th days of the study (р < 0.001) and more significant reduction in symptom intensity compared to the controls (р = 0.006). Symptom severity measured with the BCSS score decreased by 3.4 and 1.5, respectively (р = 0,006). Therapy with HFCWO was also associated with more significant improvement in oxygenation parameters and reduction in C-reactive protein (CRP) level (р = 0,001 for both). Conclusion. Therefore, treatment with HFCWO was associated to improved sputum clearance, significant improvement in clinical symptoms, earlier oxygenation improvement and CRP reduction.