ABSTRACT: Background:Mitochondrial DNA (mtDNA) has been reported to play a critical role in the progression of systemic inflammatory response syndrome (SIRS). The pathophysiology of acute respiratory distress syndrome (ARDS) is mainly attributed to the diffuse injury of alveolar epithelial cells caused by dysregulated inflammation upon direct or indirect insults. We hypothesized that plasma mtDNA may serve as an early biomarker that can predict the outcome of patients with ARDS. Methods:This study was conducted in the Department of Critical Care Medicine, Zhongda Hospital, Southeast University, a tertiary teaching hospital, from 1 May 2016 to 31 January 2017. Patients diagnosed with ARDS at admission were screened. The levels of plasma mtDNA on Day 1, Day 3 and Day 7 were detected by real-time quantitative PCR (RT-qPCR). The patients were followed-up, and all-cause mortality was recorded. The prognostic values of plasma mtDNA were evaluated in ARDS patients using receiver operating characteristic (ROC) analysis. Results:In total, 136 patients with ARDS were prospectively screened, and 73 patients were finally enrolled, with a 28-day mortality of 39.7% (29 of 73 patients). The plasma mtDNA levels at Day 7 of mild, moderate and severe ARDS patients were 1,230 (588-22,387), 5,370 (628-13,052) and 15,792 (1,623-186,814), respectively (copies/µL, P<0.05) Compared with the survivors, the level of plasma mtDNA in the nonsurvivors was significantly higher on Day 7 [67,608 (19,498-346,736) vs. 7,585 (1,717-15,792) copies/µL; P<0.05]. The AUROC of plasma mtDNA on Day 7 for predictive mortality in patients with ARDS was 0.74, and the optimal cut-off value was 18,640 copies/µL. Conclusions:Plasma mtDNA levels were positively associated with the severity of ARDS. Higher plasma mtDNA levels on Day 7 indicated a poor outcome in ARDS patients.