To investigate and evaluate if pulse oxygen saturation/fraction of inhaled oxygen (SpO2/FiO2) can be used, as replacement of arterial partial pressure of oxygen/fraction of inhaled oxygen (PaO2/FiO2), to assess oxygenation in acute respiratory distress syndrome (ARDS) patients at different high altitudes in Yunnan Province, and to find a rapid and non-invasive method for the diagnosis of ARDS at different altitudes.Patients with ARDS at different high altitudes in Yunnan Province from January 2019 to December 2020 were enrolled. The patients were divided into three groups according to different altitudes, and received different oxygen therapies according to their respective medical conditions. Group 1 consisted of patients with moderate to severe ARDS from the department of critical care medicine of the First Affiliated Hospital of Kunming Medical University (average altitude approximately 1 800 m), and received mechanical ventilation to maintain SpO2 of 0.90-0.96 with a low FiO2 for more than 30 minutes, and SpO2, FiO2, PaO2 were recorded. Group 2 consisted of patients with moderate to severe ARDS at the department of critical care medicine of People's Hospital of Diqing Tibetan Autonomous Prefecture (mean altitude about 3 200 m), and received oxygen with an attached reservoir mask to maintain SpO2 of 0.90-0.96 for 10 minutes, and then SpO2, FiO2, and PaO2 were recorded. Group 3 consisted of patients with mild to moderate-severe ARDS who admitted to the emergency department of the People's Hospital of Lijiang (average altitude approximately 2 200 m); when SpO2 < 0.90, patients received oxygen with the oxygen storage mask, and the FiO2 required to maintain SpO2 ≥ 0.90 was recorded, and SpO2, FiO2, PaO2 were recorded after oxygen inhalation for 10 minutes. Spearman coefficient was used to analyze the correlation between SpO2/FiO2 and PaO2/FiO2 in each group. Linear analysis was used to derive the linear equation between SpO2/FiO2 and PaO2/FiO2, and to evaluate arterial pH, arterial partial pressure of carbon dioxide (PaCO2), FiO2, tidal volume (VT), positive end-expiratory pressure (PEEP) and other related factors which would change the correlation between SpO2/FiO2 and PaO2/FiO2. The receiver operator characteristic curve (ROC curve) was plotted to calculate the sensitivity and specificity of using SpO2/FiO2 instead of PaO2/FiO2 to assess oxygenation of ARDS patients.Group 1 consisted of 24 ARDS patients from whom 271 blood gas analysis results were collected; group 2 consisted of 14 ARDS patients from whom a total of 47 blood gas analysis results were collected; group 3 consisted of 76 ARDS patients, and a total of 76 blood gas analysis results were collected. The PaO2/FiO2 (mmHg, 1 mmHg = 0.133 kPa) in groups 1, 2 and 3 were 103 (79, 130), 168 (98, 195) and 232 (146, 271) respectively, while SpO2/FiO2 were 157 (128, 190), 419 (190, 445) and 319 (228, 446) respectively. Among the three groups, patients in group 1 had the lowest PaO2/FiO2 and SpO2/FiO2, while patients in group 3 had the highest. Spearman correlation analysis showed that PaO2/FiO2 was highly correlated with SpO2/FiO2 in groups 1, 2 and 3 (r values were 0.830, 0.951, 0.828, all P < 0.05). Regression equation was fitted according to linear analysis: in group 1 SpO2/FiO2 = 58+0.97×PaO2/FiO2 (R2 = 0.548, P < 0.001); in group 2 SpO2/FiO2 = 6+2.13×PaO2/FiO2 (R2 = 0.938, P < 0.001); in group 3 SpO2/FiO2 = 53+1.33×PaO2/FiO2 (R2 = 0.828, P < 0.001). Further analysis revealed that PEEP, FiO2, and arterial blood pH could affect the correlation between SpO2/FiO2 and PaO2/FiO2. ROC curve analysis showed that the area under ROC curve (AUC) was 0.848 and 0.916 in group 1 with moderate to severe ARDS; based on the regression equation, the corresponding SpO2/FiO2 cut-off values at a PaO2/FiO2 of 100 mmHg and 200 mmHg were 155, 252 with a sensitivity of 84.9% and 100%, specificity of 87.2% and 70.6%, respectively. Patients with moderate to severe ARDS in group 2 (AUC was 0.945 and 0.977), the corresponding SpO2/FiO2 cut-off values at PaO2/FiO2 of 100 mmHg and 200 mmHg were 219 and 432 with the sensitivity of 100% and 85.2%, specificity of 82.5% and 100%, respectively. Patients with mild to moderate-severe ARDS in group 3 (AUC was 0.903 and 0.936), the corresponding SpO2/FiO2 cut-off values at a PaO2/FiO2 of 200 mmHg and 300 mmHg were 319 and 452 with the sensitivity of 100% and 100%, specificity of 80.9% and 86.2%, respectively.SpO2/FiO2 and PaO2/FiO2 in ARDS patients at different high altitudes in Yunnan Province have a good correlation, and non-invasive SpO2/FiO2 can be used to replace PaO2/FiO2 to assess the oxygenation in ARDS patients.