The usual method of weaning mechanically ventilated patients from high FIO2 in our ICU, in which housestaff ordered all ventilator changes in an unstandardized manner (control group), was compared to a nurse-directed protocol that used a single arterial blood gas (ABG) analysis and multiple pulse oximetry measurements. The protocol required an ABG to be obtained upon the initiation of intubation/mechanical ventilation, followed by pulse oximetry measurements obtained in accordance with a standardized timetable. Decreases in FIO2 were guided by these results. It was concluded that a nurse-directed oxygen weaning protocol utilizing a combination of a single ABG and multiple pulse oximetry measurements was safe, reduced the need for ABGs, and decreased the duration of patient exposure to toxic oxygen concentrations.