Background: It is very important to assess the effectiveness of prone positioning (PP) in patients with severe acute respiratory distress syndrome (ARDS). However, it is difficult to identify patients who may benefit from PP. The purpose of this study was to investigate whether prone positioning potential (PPP) can be predicted by lung ultrasound in patients with ARDS. Methods: In this prospective study, 45 patients with ARDS were included for the assessment of PPP. A PP lung ultrasound examination (PLUE) protocol was performed in the dorsal regions of the lung in 16 areas at H0, H3, and H6 (0, 3, and 6 h after PP). The ultrasonography videos were blindly evaluated by two expert clinicians to classify the lung regions as normal pattern (N), moderate loss of lung aeration (B1), severe loss of lung aeration (B2), and consolidation (C). The aeration scores were collected at H0, H3, and H6. According to the ratio of partial pressure of arterial oxygen to fraction of inspired oxygen (P/F ratio) at 7 days, patients were classified into PPP-positive (P/F ratio >300) and PPP-negative groups; also, the patients were classified into survival and nonsurvival groups according to 28-day mortality. Results: Aeration scores was compared at H0, H3, and H6. The scores were significantly reduced between H3 and H0, but there was no difference between H3 and H6. The aeration score variation (ASV) of the PPP-positive group between H3 and H0 was significantly higher than that in the PPP-negative group, and the sensitivity and specificity of ASV ≥5.5 for the PPP-positive group were 73.9% and 86.4%, respectively. The area under the receiver operating characteristic curve (AUROC) was 0.852 for the ASV. The ASV between H3 and H0 in the survival group was significantly higher than in the nonsurvival group. The sensitivity and specificity of ASV ≥7 for survival were 51.5% and 75%, respectively. The AUROC was 0.702 for the ASV. Conclusions: The PLUE protocol can be used to predict PPP and assess prognosis in patients with ARDS. © 2016 The Author(s).