Acute respiratory distress syndrome (ARDS) is an acute lung injury associated with high morbidity and mortality. This study aimed to establish an accurate prediction model for mortality risk in ARDS. 70% of patients from the Medical Information Mart for Intensive Care Database (MIMIC-III) were selected as the training group, and the remaining 30% as the testing group. Patients from a Chinese hospital were used for external validation. Univariate and multivariate regressions were used to screen the independent predictors. The receiver operating characteristic curve (ROC) analysis, the Hosmer-Lemeshow test, and the calibration curve were used for evaluating the performance of the model. Age, hemoglobin, heart failure, renal failure, Simplified Acute Physiology Score II (SAPS II), immune function impairment, total bilirubin (TBIL), and PaO/FiO were identified as independent predictors. The algorithm of the prediction model was: ln (Pr/(1 + Pr)) = -3.147 + 0.037 ∗ age - 0.068 ∗ hemoglobin + 0.522 ∗ heart failure (yes) + 0.487 ∗ renal failure (yes) + 0.029 ∗ SAPS II + 0.697 ∗ immune function impairment (yes) + 0.280 ∗ TBIL (abnormal) - 0.006 ∗ PaO/FiO (Pr represents the probability of death occurring). The AUC of the model was 0.791 (0.766-0.816), and the internal and the external validations both confirmed the good performance of the model. A nomogram for predicting the risk of death in ARDS patients was developed and validated. It may help clinicians early identify ARDS patients with high risk of death and thereby help reduce the mortality and improve the survival of ARDS.