Objective: This study is aimed to assess the significance of bilateral lung opacities in the definition of ARDS. Methods: A prospective, multi-center study entitled, "Validation of Simplified Acute Physiology Score 3 in Korean Intensive Care Units (ICUs)" (VSKI), performed in 22 ICUs from July 1, 2010, through January 31, 2011. Two risk-stratification methods were used to compare acute hypoxemic respiratory failure (AHRF) patients with and without bilateral lung opacities. A total of 790 patients with a ratio of arterial oxygen tension/fraction of inspired oxygen ratio (PaO2/FiO2) ＜300 mmHg on admission to ICU were included. About 154 of these patients met the criteria for the Berlin definition of ARDS, while the remaining 636 patients who had PaO2/FiO2 ＜300 mmHg but unilateral or no lung opacities were classified as cases of non-ARDS AHRF. Results: The 60-day mortality rate of ARDS patients (36.7%) was not significantly different from that of non-ARDS AHRF patients (32.3%) (P=0.57). Multivariate analysis indicated that bilateral lung opacities were not associated with increased 60-day mortality when independent predictors for 60-day mortality and propensity score were considered. In the case-control study, the 60-day mortality rate was 39.2% in the ARDS group and 27.5% in the non-ARDS AHRF group. Lower baseline hypoxemia was associated with increased mortality. Conclusions: The presence of bilateral lung opacities does not have a significant impact on mortality in patients with AHRF. Objective: This study is aimed to assess the significance of bilateral lung opacities in the definition of ARDS. Methods: A prospective, multi-center study entitled, "Validation of Simplified Acute Physiology Score 3 in Korean Intensive Care Units (ICUs)" (VSKI), performed in 22 ICUs from July 1, 2010, through January 31, 2011. Two risk-stratification methods were used to compare acute hypoxemic respiratory failure (AHRF) patients with and without bilateral lung opacities. A total of 790 patients with a ratio of arterial oxygen tension/fraction of inspired oxygen ratio (PaO2/FiO2) ＜300 mmHg on admission to ICU were included. About 154 of these patients met the criteria for the Berlin definition of ARDS, while the remaining 636 patients who had PaO2/FiO2 ＜300 mmHg but unilateral or no lung opacities were classified as cases of non-ARDS AHRF. Results: The 60-day mortality rate of ARDS patients (36.7%) was not significantly different from that of non-ARDS AHRF patients (32.3%) (P=0.57). Multivariate analysis indicated that bilateral lung opacities were not associated with increased 60-day mortality when independent predictors for 60-day mortality and propensity score were considered. In the case-control study, the 60-day mortality rate was 39.2% in the ARDS group and 27.5% in the non-ARDS AHRF group. Lower baseline hypoxemia was associated with increased mortality. Conclusions: The presence of bilateral lung opacities does not have a significant impact on mortality in patients with AHRF.