Adaptive support ventilation (ASV) is a fully automated closed-loop ventilation mode that can act as pressure support (PS) and pressure-controlled ventilation. The aim of this study was to evaluate the benefits of using ASV in the initiation, maintenance, and weaning phases of the mechanical ventilation in comparison with synchronized intermittent mandatory ventilation (SIMV)+PS mode in patients with chronic obstructive pulmonary disease (COPD). Sixty patients with COPD requiring mechanical ventilation were recruited in this study. Among them, 37 patients were treated by SIMV+PS, whereas 23 patients were assigned for ASV. After resolution of the cause of acute respiratory failure, assessment of readiness for weaning was done. Patients were followed after 30, 60 min, and 24 h. Ventilator and hospital outcomes were recorded. Compared with SIMV+PS, ASV provided shorter weaning time (27.3 ± 12.3 vs. 62 ± 14.1 h). Moreover, there was a shorter hospital stay of 14.83 ± 6.14 for ASV group compared with 22.14 ± 17.39 days for SIMV+PS, with similar weaning failure rates, death rate, and intubation period in both groups. This study proved that ASV mode was successful as a mode of initiation, maintenance, and weaning in acute exacerbation of patients with COPD requiring mechanical ventilation with a shorter weaning time and shorter hospital stay compared with SIMV+PS mode.