Introduction: Increased work of breathing causing inspiratory muscle fatigue can delay extubation. Aim: This study compared the time taken for extubation in patients admitted with acute respiratory failure and ventilated with assist control mode (ACV) of ventilation or synchronised intermittent mandatory ventilation and Pressure Support (SIMV-PS). Patients and Methods: This was an observational study conducted in medical and surgical intensive care unit of a tertiary care hospital in South India. Patients receiving invasive mechanical ventilation for more than 24 hours were enrolled into the study. Demographic data, ventilator settings, ABG values after initiation of mechanical ventilation and before extubation, change of initial mode were recorded. The primary outcome was to determine the difference in the time taken for extubation (hours). Result: A total of 34 subjects were enrolled, twenty in SIMV-PS and fourteen subjects in ACV. The median age of the subjects was 53 years, 23 (68%) were males and 11 (32%) were females. The median (interquartile range) of Acute Physiology and Chronic Health Evaluation II (APACHE II) score was 18.5 (14, 29). Majority had a diagnosis of sepsis (23.5%) and pneumonia (17.6%). The median time on mechanical ventilation in SIMV-PS group was 90 h (57, 133) and in ACV group was 131 h (64, 258). There were also no statistical differences in the duration of weaning (p). Conclusion: Mechanical ventilation with assist control mode of ventilation or synchronised intermittent mandatory ventilation and pressure support are comparable in the time to weaning patients off ventilator.