Background: Acute respiratory distress syndrome (ARDS) is an increasingly common acute respiratory failure that seriously threaten people's health. ARDS has a case fatality rate of up to 40%. ARDS is a serious threat to the life safety of patients and the quality of life, causing a huge economic burden to individuals, families and society. ARDS has become a large worldwide public health problem. Prone position ventilation (PPV) is an important auxiliary treatment for ARDS, which could improve oxygenation. However, PPV could cause Pressure injuries (PI) and other complications easily. We found that 45 degrees PPV could reduce the incidence of PI, but lack of robust Evidence-based medicine evidence proving its efficacy. Therefore, we designed a randomized controlled trial to evaluate the efficacy of 45 degrees PPV in the treatment of ARDS. Methods: A total of 268 patients will be randomly assigned to the control group and the test group (n = 134 each) in a ratio of 1:1. The treatment period is 7 days. The primary outcome measure will be the incidence of PI. The secondary outcomes will include APACHE II score, Braden Scale score, heart rate, systolic blood pressure, diastolic blood pressure, central venous pressure, mean arterial pressure, pH of arterial blood, oxygenation index, oxygen partial pressure, and carbon dioxide partial pressure. The evaluation will be performed at baseline, 1 hour, 12 hour, 48 hour, 5days, 7days after PPPV. Results: This study is helpful to evaluate the efficacy of 45 degrees PPV in the treatment of ARDS. Conclusion: 45 degrees PPV may reduce the incidence of PI and improve oxygenation in patients with ARDS, which has important value in practical application