Acute Respiratory Distress Syndrome (ARDS) is a severe condition with high mortality and morbidity rates. Evidence on the effectiveness of pharmacological interventions for ARDS treatment is limited. Recent studies suggest that aspirin may prevent ARDS development, but its efficacy in established ARDS is uncertain.We enrolled patients with ARDS using data from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database. Primary outcomes were 30- and 90-day mortality rates and length of ICU stay. We employed multivariable Cox regression and linear regression models for statistical analysis and used propensity score matching (PSM) to ensure robust results.The study included 10,042 participants with an average age of 61.8 ± 15.3 years. Kaplan-Meier analysis showed significantly lower 30- and 90-day mortality rates in patients treated with pre-ICU admission aspirin compared with non-aspirin use (p < 0.0001). Multivariable Cox regression models revealed a significant 63% reduction in 30-day mortality for pre-ICU aspirin users (HR = 0.37, 95% CI: 0.31-0.44, p < 0.001). Aspirin use in the ICU was associated with a 59% reduction in ICU mortality and a 0.68-day reduction in length of ICU stay (p < 0.05). These findings consistently indicate that aspirin may improve survival in patients with ARDS, even after further stratification of aspirin use and PSM analysis.Our findings suggest that aspirin treatment before ICU admission is associated with significantly reduced 30- and 90-day mortality rates and decreased length of ICU stay in patients with ARDS.Copyright © 2024. Published by Elsevier Ltd.