Background <p>Acute respiratory distress syndrome (ARDS) is a prevalent critical condition encountered in clinical settings and is characterized by high mortality. This research investigated miR-99a in diagnosing ARDS and its role in predicting pulmonary fibrosis (PF) among ARDS patients, to identify novel and effective biomarkers for ARDS.</p> Materials and methods <p>In this study, 128 patients with ARDS were selected as the experimental group, and 98 healthy people were included as the control group. ELISA measured the expression levels of IL-6, TNF-α, and IL-8, and the expression of miR-99a was measured by qRT-PCR. ROC curve evaluated the diagnostic value of miR-99a in ARDS patients and PF. Logistic regression evaluated the independent risk factors for PF in ARDS patients.</p> Results <p>This research demonstrated that miR-99a and inflammatory factors (IL-6, TNF-α, and IL-8) were markedly elevated in ARDS patients. The expression levels of miR-99a exhibited a significant correlation with the Murray score, PaO2/FiO2 ratio, APACHE II score, and occurrence of PF in ARDS patients. Furthermore, miR-99a displayed a robust distinguishing capacity for ARDS patients. Notably, miR-99a was found to be highly expressed within the PF subgroup of ARDS patients. It was recognized as a critical risk factor for PF occurrence in ARDS individuals and demonstrated considerable predictive potential.</p> Conclusion <p>The miR-99a could potentially be a promising biomarker for ARDS and predict the risk of PF in ARDS patients.</p>