We evaluated the sensitivity of the arterial/alveolar oxygen tension ratio (PaO2/PAO2) when used in an equation to predict the inspired oxygen concentration (FIO2) needed for a desired arterial oxygen tension (PaO2). We reviewed at random 100 paired sets of arterial blood gas data obtained before and after an FIO2 change from 41 mechanically ventilated patients. Our analysis demonstrated that the new FIO₂ was accurately predicted by the equation if the PaO2/PAO2 changed ≤ 0.05 after the FIO2 change (r = 0.95). Using a PaO2/PAO2 that changed by > 0.05 resulted in poor prediction of the new FIO2 (r = 0.47). We conclude that it is possible to use the PaO2/PAO2 to accurately predict the FIO2 needed for a desired PaO2 if the PaO2/PAO2 does not change > 0.05 after an FIO2 change. In an unstable patient, in whom the PaO2/PAO2 may change after a change in FIO2, the predicted FIO2 should be used with prudence. The calculation should further be supported by serial recording of the PaO2/PAO2 and by thorough clinical evaluation.