OBJECTIVE: To investigate the impact of high-frequency chest wall oscillation in chronic obstructive pulmonary disease patients with infective exacerbation. DESIGN: Clinical randomized controlled trial. SETTING: Patients received high-frequency chest wall oscillation therapy at the Department of Pulmonology. SUBJECTS: Stage III-IV chronic obstructive pulmonary disease patients hospitalized with acute infective exacerbation who had received high-frequency chest wall oscillation therapy were studied. INTERVENTIONS: Patients were randomized into two groups, which were classified as I and II. All patients have been treated with bronchodilators, antibiotics, if necessary oxygen and patient education, as part of acute chronic obstructive pulmonary disease exacerbation protocol. Group II patients received additional high-frequency chest wall oscillation therapy. MAIN MEASURES: Body mass index (B), forced expiratory volume in the first second (O), modified Medical Research Council dyspnea scale (D) and 6-minute walking test (E) (BODE) index, forced expiratory volume in the first second, dyspnea, exercise capacity, oxygenation parameters and hospitalization of duration were recorded at baseline and at three-days and five-days follow-up. RESULTS: From April 2009 to July 2011, a total of 99 patients were assessed for eligibility, 50 patients were enrolled and randomized into two groups. A total of 50 (100%) patients (25 in Group I and 25 in Group II) were followed up for five days. Application of high-frequency chest wall oscillation therapy resulted in no significant advantage in all outcomes (p > 0.05). Mean (SD) baseline BODE index value in Group I was 7.72 (1.76), in Group II was 7.72(1.89) (p = 0.55). On the fifth-day assessment, mean (SD) BODE index value in Group I was 7.24 (1.83), in group II was 6.44 (2.46) (p = 0.18). CONCLUSIONS: The application of high-frequency chest wall oscillation therapy offers no additional advantages on infective exacerbations in chronic obstructive pulmonary disease.