The initial hypoxemic level of acute respiratory distress syndrome (ARDS) defined according to Berlin definition might not be the optimal predictor for prognosis. We aimed to determine the predictive validity of the stabilized ratio of partial pressure arterial oxygen and fraction of inspired oxygen (PaO2/FiO2 ratio) following standard ventilator setting in the prognosis of patients with ARDS.This prospective observational study was conducted in a single tertiary medical center in Taiwan and compared the stabilized PaO2/FiO2 ratio (Day 1) following standard ventilator settings and the PaO2/FiO2 ratio on the day patients met ARDS Berlin criteria (Day 0). Patients admitted to intensive care units and in accordance with the Berlin criteria for ARDS were collected between December 1, 2012 and May 31, 2015. Main outcome was 28-day mortality. Arterial blood gas and ventilator setting on Days 0 and 1 were obtained.A total of 238 patients met the Berlin criteria for ARDS were enrolled, and they were classified as mild (n = 50), moderate (n = 125), and severe (n = 63) ARDS, respectively. Twelve (5%) patients who originally were classified as ARDS did not continually meet the Berlin definition, and a total of 134 (56%) patients had the changes regarding the severity of ARDS from Day 0 to Day 1. The 28-day mortality rate was 49.1%, and multivariate analysis identified age, PaO2/FiO2 on Day 1, number of organ failures, and positive fluid balance within 5 days as significant risk factors of death. Moreover, the area under receiver-operating curve for mortality prediction using PaO2/FiO2 on Day 1 was significant higher than that on Day 0 (P = 0.016).PaO2/FiO2 ratio on Day 1 after applying mechanical ventilator is a better predictor of outcomes in patients with ARDS than those on Day 0.