Background: Endotracheal tube suctioning (ETS) is one of the most frequent procedures performed by nurses in intensive care units. Nevertheless, some suctioning practices are still being performed that do not provide any benefit for patients. Objectives: To investigate the effects of minimally invasive ETS (MIETS) versus routine ETS (RETS) on physiological indices in adult intubated patients. Methods: In this single centre parallel randomised controlled, open label trial, 64 adult intubated patients in the four intensive care units of Alzahra University hospital, Isfahan, Iran, were randomly allocated to a MIETS or a RETS group. Physiological indices including systolic blood pressure, diastolic blood pressure, mean arterial pressure, heart rate, and peripheral oxygen saturation were assessed immediately before, immediately after, and 10 min after ETS in both groups. The chi-square test, independent t-test, and repeated measures analysis of variance were used to analyse the data. Results: Sixty-four patients were randomised and analysed. There were no significant differences in mean heart rate between the both groups across the three time points. However, there was a significant drop in peripheral oxygen saturation across the three time points in the RETS group compared to the MIETS group. Furthermore, there was a significant increase in systolic blood pressure, diastolic blood pressure, and mean arterial pressure across the three time points in the RETS group compared to the MIETS group. Conclusion: The results of this study indicate that the use of MIETS has less effect on the alterations of physiological indices and consequently fewer adverse effects than RETS.