Purpose: PaO 2 to FiO 2 ratio (P/F) is used to assess the degree of hypoxemia adjusted for oxygen requirements. The Berlin definition of Acute Respiratory Distress Syndrome (ARDS) includes P/F as a diagnostic criterion. P/F is invasive and cost-prohibitive for resource-limited settings. SaO 2 /FiO 2 (S/F) ratio has the advantages of being easy to calculate, noninvasive, continuous, cost-effective, and reliable, as well as lower infection exposure potential for staff, and avoids iatrogenic anemia. Previous work suggests that the SaO 2 /FiO 2 ratio (S/F) correlates with P/F and can be used as a surrogate in ARDS. Quantitative correlation between S/F and P/F has been verified, but the data for the relative predictive ability for ICU mortality remains in question. We hypothesize that S/F is noninferior to P/F as a predictive feature for ICU mortality. Using a machine-learning approach, we hope to demonstrate the relative mortality predictive capacities of S/F and P/F., Methods: We extracted data from the eICU Collaborative Research Database. The features age, gender, SaO 2 , PaO 2 , FIO 2 , admission diagnosis, Apache IV, mechanical ventilation (MV), and ICU mortality were extracted. Mortality was the dependent variable for our prediction models. Exploratory data analysis was performed in Python . Missing data was imputed with Sklearn Iterative Imputer. Random assignment of all the encounters, 80% to the training ( n = 26690) and 20% to testing ( n = 6741), was stratified by positive and negative classes to ensure a balanced distribution. We scaled the data using the Sklearn Standard Scaler. Categorical values were encoded using Target Encoding. We used a gradient boosting decision tree algorithm variant called XGBoost as our model. Model hyperparameters were tuned using the Sklearn RandomizedSearchCV with tenfold cross-validation. We used AUC as our metric for model performance. Feature importance was assessed using SHAP, ELI5 (permutation importance), and a built-in XGBoost feature importance method. We constructed partial dependence plots to illustrate the relationship between mortality probability and S/F values., Results: The XGBoost hyperparameter optimized model had an AUC score of .85 on the test set. The hyperparameters selected to train the final models were as follows: colsample_bytree of 0.8, gamma of 1, max_depth of 3, subsample of 1, min_child_weight of 10, and scale_pos_weight of 3. The SHAP, ELI5, and XGBoost feature importance analysis demonstrates that the S/F ratio ranks as the strongest predictor for mortality amongst the physiologic variables. The partial dependence plots illustrate that mortality rises significantly above S/F values of 200., Conclusion: S/F was a stronger predictor of mortality than P/F based upon feature importance evaluation of our data. Our study is hypothesis-generating and a prospective evaluation is warranted. Take-Home Points . S/F ratio is a noninvasive continuous method of measuring hypoxemia as compared to P/F ratio. Our study shows that the S/F ratio is a better predictor of mortality than the more widely used P/F ratio to monitor and manage hypoxemia., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Sharad Patel et al.)