Aims and background: Endotracheal tube cuff pressure (ETCP) is an important factor to determine the development of complications associated with invasive mechanical ventilation. To avoid preventable complications arising out of immobilization, frequent changes in body positioning are necessary. Such variations in body position can affect ETCP in critically ill patients who are on mechanical ventilation. So, our study aimed to assess the effect of changes in body position on ETCP in patients who are on mechanical ventilation. Materials and methods: This prospective observational study included 31 critically ill intubated patients. Each study subject was first placed in a neutral starting position with a 30° head elevation. Then, they were subjected to a sequential change in body position based on the 16 most used positions as part of the critical care unit's (CCUs) daily routine. Endotracheal tube cuff pressure was measured after each position change. Data were analyzed using standard statistical tests. Results: Statistically significant difference in ETCP was observed during anteflexion of neck, hyperextension of neck, left lateral flexion of neck, right lateral flexion of neck, left lateral rotation of neck, right lateral rotation of neck, 10^o recumbent position, supine position, Trendelenburg position, and right lateral 30° and 45° positions. Maximum increase in ETCP was seen during anteflexion of neck (31 ± 4.5; 22–42 cm H₂O). Conclusion: Our study demonstrates significant deviations in ETCP from the recommended range following changes in the body position of mechanically ventilated patients, highlighting the need for the measurement of ETCP after each position change and maintenance of the same within the target range.