BACKGROUND: At present, understanding of the most effective ventilation methods for treating chronic obstructive pulmonary disease (COPD) patients experiencing acute worsening symptoms and respiratory failure remains relatively limited. This report analyzed the efficiency and side effects of various ventilation techniques used for individuals experiencing an acute COPD exacerbation. AIM: To determine whether pressure-controlled ventilation (PCV) can lower peak airway pressures (PAPs) and reduce the incidence of barotrauma compared to volume-controlled ventilation (VCV), without compromising clinical outcomes and oxygenation parameters. METHODS: We have evaluated 600 patients who were hospitalized due to a severe COPD exacerbation, with 400 receiving mechanical ventilation for the respiratory failure. The participants were divided into two different groups, who were administered either VCV or PCV, along with appropriate management. We thereafter observed patients' attributes, clinical factors, and laboratory, radiographic, and arterial blood gas evaluations at the start and during their stay in the intensive care unit (ICU). We have also employed appropriate statistical methods for the data analysis. RESULTS: Both the VCV and PCV groups experienced significant enhancements in the respiratory rate, tidal volume, and arterial blood gas values during their time in the ICU. However, no significant distinctions were detected between the groups in terms of oxygenation indices (partial pressures of oxygen/raction of inspired oxygen ratio) and partial pressures of carbon dioxide improvements. There was no considerable disparity observed between the VCV and PCV groups in the hospital mortality (32% vs 28%, P = 0.53), the number of days of ICU stay [median interquartile range (IQR): 9 (6-14) d vs 8 (5-13) d, P = 0.41], or the duration of the mechanical ventilation [median (IQR): 6 (4-10) d vs 5 (3-9) d, P = 0.47]. The PCV group displayed lower PAPs compared to the VCV group (P < 0.05) from the beginning of mechanical ventilation until extubation or ICU departure. The occurrence of barotrauma was considerably lower in the PCV group in comparison to the VCV group (6% vs 16%, P = 0.03). CONCLUSION: Both VCV and PCV were found to be effective in treating patients with acute COPD exacerbation. However, PCV was associated with lower PAPs and a significant decrease in barotrauma, thus indicating that it might be a safer ventilation method for this group of patients. However, further large-scale study is necessary to confirm these findings and to identify the best ventilation approach for patients experiencing an acute COPD exacerbation.