BACKGROUND There is need to identify biomarkers for prognosis of acute respiratory distress syndrome (ADRS). This may allow early and accurate identification of patients with high-risk ARDS to guide adjustment of clinical treatment and nursing intervention, which would ultimately improve prognosis of patients with ARDS. Biomarkers based on a combination of fasting glucose and lymphocyte counts to predict prognosis in critically ill patients with ARDS remain undefined. In this study, we investigated the association between glucose-to-lymphocyte ratio (GLR) and in-hospital mortality. METHODS The study obtained data from Medical Information Mart for Intensive Care-IV (MIMIC-IV Version 1.0) database. We defined the GLR as fasting glucose/lymphocyte count and the patient in-hospital mortality was considered as the outcome. In addition, we employed linear and logistic regression models for analysis. RESULTS In total, 1,085 patients with ARDS were included in this study. The eligible participants included 498 female and 587 males, with a mean age of 64.2 ± 17.5 years. Logistic regression analysis demonstrated that higher GLR was an independent risk factor for all-cause mortality (OR =1.67, 95% CI: 1.26-2.22) after adjusting for age, sex, anion gap, white blood cell count, congestive heart failure, sequential organ failure assessment (SOFA), SBP, DBP, and respiratory rate in both the dichotomized group and subgroups. We also analyzed the in-hospital mortality to ROC curves by comparing the value between SOFA + GLR and SOFA. The area under the curve (AUC) was 0.6991 for the SOFA + GLR (95% CI: 0.6634-0.7348), and 0.6613 for the SOFA (95% CI: 0.6238-0.6988). CONCLUSIONS Our data showed that the GLR was an independent predictor of in-hospital mortality for patients with ARDS. The GLR is an integrated, readily available clinical biomarker for mortality in patients with ARDS.