There are few recommendations on how best to apply certain modes of mechanical ventilation. The application of Airway Pressure Release Ventilation (APRV) includes strategic implementation of specific inspiratory times (I-times) and particular mean airway pressures (MAWP) neither of which is standardized. This study utilized a retrospective analysis of archived electronic health record data to evaluate the clinical outcomes of adult patients that had been placed on APRV for at least 8 hours. 68 adult subjects were evaluated as part of a convenient purposive sample. All outcomes of interest (surrogates) for short-term clinical outcomes to include the PaO2/FiO2 (P/F) ratio, Oxygen Index and Oxygen Saturation Index (OI; OSI), and Modified Sequential Organ Failure Assessment (MSOFA) scores showed improvement after at least 8 hours on APRV. Most notably, there was significant improvement in P/F ratio (p = .012) and OSI (p = .000). Results of regression analysis showed P low as a statistically significant negative predictor of pre-APRV P/F ratio with a higher initial P low coinciding with a lower P/F ratio. The regression analysis also showed MAWP as a significant positive predictor of post-APRV OSI and P high and P low as significant negative predictors of post-APRV MSOFA scores. In summary, it was found that settings for P high, Plow, and T low in addition to overall MAWP and Body Mass Index (BMI) had significant correlation to impact at least one of the short-term clinical outcomes measured.