Background: There is limited research into the utility of average volume-assured pressure support (AVAPS), a volume-assured pressurecontrolled mode, especially in patients with hypercapnic respiratory failure. Aims: This study aimed at a randomized comparison of AVAPS and bilevel positive airway pressure spontaneous/timed (BPAP S/T) modes in non-invasive mechanical ventilation (NIMV) application with hypercapnic respiratory failure patients in the emergency department (ED). Study Design: Randomized controlled study. Methods: In this prospective randomized controlled study, 80 patients admitted to ED with hypercapnic respiratory failure requiring NIMV were randomly assigned to AVAPS or S/T groups using the sealed envelope method (33 patients in the S/T group, 47 patients in the AVAPS group). Data of arterial blood gas (ABG), vital parameters, Glasgow Coma Score (GCS), additional treatment needs, and clinical outcomes were evaluated, and the treatment success rates of both groups were compared. Results: A total of 80 patients, 33 in the S/T and 47 in the AVAPS group, were analyzed in the study. The pH values improved in the AVAPS group compared to the baseline (0.07 [0.04-0.10] vs 0.03 [0.00-0.11]). PaCO2 (partial pressure of carbon dioxide) excretion was faster in the AVAPS group than in the S/T group in the first hour (10.20 mmHg [6.20-19.20] vs. 4.75 ([-] 0.83-16.88)). The comparison of blood gas measurements showed no significant differences between the groups regarding the changes in PaCO2 and pH values over time (P = .141 and P = .271, respectively). During the ED follow-up, 3 (6.4%) patients in the AVAPS group and 5 (15.2%) patients in the S/T group needed intubation [Relative risk: 0.42 (95% CI: 0.11 to 1.64), P = .21]. Conclusion: In this study, improvements in blood gas parameters in the AVAPS group were faster compared to the S/T group; however, we did not find any significant difference between the groups in terms of clinical parameters. The AVAPS mode is as effective and safe as BPAP S/T in treating patients with hypercapnic respiratory failure in the ED.