Endotracheal suctioning is a common aspect of nursing care to mechanically-ventilated patients. The aim of this study was to investigate the effects of two suctioning techniques on oxygen saturation (SaO2) and the amount of drained secretions. A quasi-experimental study of 103 mechanically-ventilated patients was conducted from two tertiary hospitals in Greece. Two suctioning techniques were applied to each patient: with normal saline instillation and without. Normal saline instillation was associated with increased secretions' weight (p<0.001) and no significant differences in SaO2 values compared with no instillation. In examining each suctioning technique separately, the use of normal saline instillation was associated with a decrease in SaO2 levels 1 minute (p<0.001) and 15 minutes (p=0.002) after this procedure. In addition, suctioning without normal saline instillation was associated with a decrease in SaO2 1 minute (p<0.001) after the suction. In conclusion, normal saline instillation is related with a negative outcome on patient oxygenation for a prolonged period after the suction and causes the removal of a greater amount of secretions than the applied technique with no instillation. Comparing the two techniques, none is superior to the other resulting from the statistically insignificant comparative differences in SaO2 values.