Background:Patients with severe hypercapnia represent a particularly serious condition in an emergency department (ED), requiring immediate attention. Noninvasive ventilation (NIV) is an integral part of the treatment for acute respiratory failure. The present study aimed to validate the measurement of end-tidal CO 2 (EtCO 2 ) as a noninvasive technique to evaluate the effectiveness of NIV in acute hypercapnic respiratory failure. Methods: Twenty consecutive patients admitted to the ED with severe dyspnea were enrolled in the study. NIV by means of bilevel positive airway pressure, was applied to the patients simultaneously with standard medical therapy and continued for 12 hours; the arterial blood gases and side-stream nasal/oral EtCO 2 were measured at subsequent times: T0 (admission to the ED), T1h (after 1 hour), T6h (after 6 hours), and T12h (after 12 hours) during NIV treatment. Results: The arterial CO 2 partial pressure (PaCO 2 )-EtCO 2 gradient decreased progressively, reaching at T6h and T12h values lower than baseline (P , 0.001), while arterial pH increased during the observation period (P , 0.001). A positive correlation was found between EtCO 2 and PaCO 2 values (r = 0.89, P , 0.001) at the end of the observation period. Conclusion: In our hypercapnic patients, the effectiveness of the NIV was evidenced by the progressive reduction of the PaCO 2 -EtCO 2 gradient. The measurement of the CO 2 gradient could be a reliable method in monitoring the effectiveness of NIV in acute hypercapnic respiratory failure in the ED.