Abstract: Objective To investigate the effect of methylprednisolone doses on the therapeutic outcome of bilevel positive airway pressure ventilation (BiPAP) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) complicated with type II respiratory failure. Methods The clinical data of patients with AECOPD complicated with type II respiratory failure were analyzed retrospectively. Patients were divided into a control group and an experimental group, with 102 cases in each, using propensity score matching. All patients received conventional therapy combined with BiPAP. On this basis, the control group was administered 40 mg methylprednisolone intravenously once a day, while the experimental group was administered 80 mg methylprednisolone intravenously once a day. Both groups were treated continuously for 7 days. Changes in arterial blood gas parameters, tidal breathing lung function indicators, and laboratory inflammatory markers and indices before and after treatment were compared between the two groups. Clinical outcome and the incidence of adverse drug reactions were recorded. Results After treatment, there were no significant differences in arterial blood gas parameters (pH value, partial pressure of arterial oxygen, partial pressure of arterial carbon dioxide, arterial oxygen saturation) between the two groups (all P＞0.05). The peak expiratory flow and tidal expiratory flow at 50% of tidal volume in the experimental group were significantly higher than those in the control group. Furthermore, the serum levels of interleukin-6, high-sensitivity C reactive protein, and neutrophil-to-lymphocyte ratio were significantly lower than those in the control group (all P＜0.05). There were no significant differences in the length of hospital stay, tracheal intubation rate, or 28-day mortality between the two groups (all P＞0.05). However, the total incidence of adverse reactions in the experimental group was significantly higher than that in the control group (all P＜0.05). Conclusion Compared with the 40 mg dose, 80 mg methylprednisolone can more effectively improve lung function and suppress the systemic inflammatory response in patients with AECOPD complicated with type II respiratory failure, but it increases the risk of adverse drug reactions.