Objective This study aimed to examine the use of point-of-care ultrasonography (POCUS) in detecting diaphragmatic dysfunction (DD) and evaluate its ability to predict noninvasive mechanical ventilation (NIV) failure in patients presented to the emergency department with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Methods In this prospective cohort study, the diaphragm was examined using POCUS in patients with AECOPD. DD was defined as a diaphragm thickening fraction of less than 20% during spontaneous breathing. NIV failure was the primary outcome of the study, and duration of hospital stay and in-hospital mortality were the secondary outcomes. Specificity, sensitivity, positive predictive value, and negative predictive value were estimated for predicting NIV failure in DD and evaluating the diagnostic performance of POCUS. Results 60 patients were enrolled the study. NIV failure was found in 11 (73.3%) of 15 patients with DD and in 2 (4.4%) of 45 patients without DD. In predicting NIV failure, DD had a sensitivity of 84.6% (95% confidence interval [CI]:54.6–98.1), specificity of 91.5% (95% CI:79.6–97.6), positive predictive value of 73.3% (95% CI:51.2–87.8), and negative predictive value of 95.6% (95% CI:85.7–98.7). The duration of hospital stay was not different between groups (p = .065). No in-hospital mortality was seen in patients without DD. Conclusions DD has high sensitivity and specificity in predicting NIV failure in patients admitted to the emergency department with AECOPD. DD can be assessed by an experienced clinician noninvasively using POCUS in emergency departments.