Background: The goal of this study was to investigate the effects of pulmonary static inflation with 50% xenon on postoperative oxygen impairment during cardiopulmonary bypass (CPB) for Stanford type A acute aortic dissection (AAD). Methods: This prospective single-center nonrandomized controlled clinical trial included 100 adult patients undergoing surgery for Stanford type A AAD at an academic hospital in China. Fifty subjects underwent pulmonary static inflation with 50% oxygen from January 2013 to January 2014, and 50 underwent inflation with 50% xenon from January 2014 to December 2014. During CPB, the lungs were inflated with either 50% xenon (xenon group) or 50% oxygen (control group) to maintain an airway pressure of 5cm H2O. The primary outcome was oxygenation index (OI) value after intubation, and 10minutes and 6hours after the operation. The second outcome was cytokine and reactive oxygen species levels after intubation and 10minutes, 6hours, and 24hours after the operation. Results: Patients treated with xenon had lower OI levels compared to the control group before surgery (P= 0.002); however, there was no difference in postoperative values between the 2 groups. Following surgery, mean maximal OI values decreased by 18.8% and 33.8%, respectively, in the xenon and control groups. After surgery, the levels of interleukin-6 (IL-6), tumor necrosis factor alpha, and thromboxane B-2 decreased by 23.5%, 9.1%, and 30.2%, respectively, in the xenon group, but increased by 10.8%, 26.2%, and 26.4%, respectively, in the control group. Moreover, IL-10 levels increased by 28% in the xenon group and decreased by 7.5% in the control group. There were significant time and treatment-time interaction effects on methane dicarboxylic aldehyde (P= 0.000 and P= 0.050, respectively) and myeloperoxidase (P= 0.000 and P= 0.001 in xenon and control groups, respectively). There was no difference in hospital mortality and 1-year survival rate between the 2 groups. Conclusion: Pulmonary static inflationwith 50% xenon duringCPBcould attenuate OI decreases at the end of surgery for Stanford type A AAD. Thus, xenon may function by triggering anti-inflammatory responses and suppressing pro-inflammatory and oxidative effects.