Objective: To investigate the clinical value of non-invasive ventilation for respiratory muscle fatigue acute exacerbation of chronic obstructive pulmonary disease (AECOPD) patients without respiratory exhaustion. Methods: 138 cases respiratory muscle fatigue AECOPD patients in our hospital were randomly divided into research group and control group, 69 cases in each group. Control group were treated with antibiotics, oxygen, expectorant, maintaining electrolyte acid-base balance treatment. Research group were treated with non-invasive ventilation based on control group’s treatment. The pulmonary function, blood gas analysis results, respiratory muscle function, dyspnea level and treatment tolerance of the two groups were compared. Results: There was no significant difference in pulmonary function between the two groups before treatment (P>0.05). After treatment, FEV1, FEV1/FVC of research group were higher than that in control group (P<0.05). There was no significant difference in PO2, PCO2, SaO2, pH, which stand for blood gas analysis between the two groups, neither before treatment nor after treatment (P>0.05). The dyspnea level (mMRC score) of research group was lower than that of control group (P<0.05), while respiratory muscle function was higher (P<0.05). All patients had good tolerance for their treatment. Conclusion: Non-invasive ventilation has exact effect for respiratory muscle fatigue AECOPD patients without respiratory exhaustion. It could improve patients’ respiratory function and ease dyspnea, safeguard respiratory failure as well.