Objective To analyze the predictive value of von Willebrand factor (vWF) and acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score on severity and prognosis of acute respiratory distress syndrome (ARDS). Methods The ARDS patients who were admitted between January 2010 and May 2012 were recruited in the study. APACHEⅡ score and plasma vWF were detected on the first day and the third day after diagnose of ARDS. The patients were divided intoasurvival group andadeath group according the prognosis. The predictive value of vWF and APACHEⅡ score on prognosis were analyzed by the receiver operating characteristic (ROC) curve. Lung injury score was calculated and its relationship with vWF and APACHEⅡ score were analyzed. Results One-hundred and twelve cases of ARDS were enrolled. There were no significant differences between the survival group and the death group in sex, age, respiration rate, blood pressure, white blood cells, procalcitonin or C-reactive protein (P > 0.05). On the first day after diagnosis of ARDS, the APACHEⅡ score and vWF level of the survival group were significantly lower than those in the death group (P < 0.05). On the third day, the APACHEⅡ score was increased but vWF level declined compared with those on the first day (P < 0.05). On the first day, lung injury score of the survival group was 1.7±0.4, significantly lower than that in the death group (2.5±0.6). On the third day, lung injury score in the survival group decreased, while lung injury score of the death group was significantly increased (P < 0.05). On the first day, vWF and APACHEⅡ score were positively correlated with lung injury score (r=0.75, P < 0.05; r=0.79, P < 0.05), respectively. On the first day, the area under the ROC curve of APACHEⅡ score and vWF were 0.87 and 0.91, respectively (P < 0.05). Conclusion APACHEⅡ score and vWF have high diagnostic value in evaluating the degree of lung injury and predicting the prognosis of patients with ARDS.