Abstract Background Mechanical ventilation (MV) causes diaphragmatic atrophy and reduces diaphragmatic efficiency. Patients with diaphragmatic dysfunction (DD) have longer MV durations and intensive care unit (ICU) stay. There is currently a scarcity of data on the effect of different modes of MV on diaphragmatic function and ultrasound-guided assessment of diaphragmatic efficiency. Methodology Sixty mechanically ventilated patients were randomly divided into four equal groups (15 each), patients were ventilated using either Assist Control Pressure Controlled mode (ACPC group)(Group A), Synchronized Intermittent Mandatory Ventilation Pressure Controlled mode (SIMV)(Group S), Bi-level Positive Airway Pressure mode (BiPAP)(Group B), or Pressure Support Ventilation mode (PSV)(Group P). The primary outcomes were diaphragmatic motion & structure in terms of Diaphragmatic Excursion (DE) & Diaphragmatic Thickness Fraction (DTF) respectively. The duration of the ICU stay was the secondary outcome. Results The PSV group had the highest DE indicating better diaphragmatic function. In addition, MV for longer durations led to diaphragmatic thinning and decreased DTF resulting in DD. Conclusion Among the various modes of ventilation employed in the study, PSV was found to be the mode with the lowest risk of DD. Trial Registry PACTR202112653971335.