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OBJECTIVE: To evaluate the comparative efficacy and safety of inhaled sedation versus intravenous (IV) sedation in adults with acute respiratory distress syndrome (ARDS) undergoing invasive mechanical ventilation. METHODS: A systematic search was conducted in PubMed, MEDLINE, Embase, and the Cochrane Library from inception until November 2025. Randomized controlled trials (RCTs) and observational studies that compared inhaled anesthetics (sevoflurane or isoflurane) with intravenous (IV) sedatives in adults (≥18 years) diagnosed with ARDS were included. Pooled analyses were conducted using fixed- or random-effects models based on heterogeneity. RESULTS: Eight studies involving 1440 adults were included. Inhaled sedation was associated with similar short-term mortality (OR, 1.20; 95% CI, 0.94-1.55) and duration of mechanical ventilation (MD, -0.35 days; 95% CI, -4.01 to 3.32) compared with IV sedation, but With a shorter ICU lengtth of stay (MD, -2.27 days; 95% CI, -3.75 to -0.80).PaO2/FiO2 improved in analyses driven by Sevoflurane-containing studies (MD, 39.7 mmHg; 95% CI, 10.44-68.95). Sevoflurane was also associated with a higher risk of acute kidney injury (AKI) (OR, 1.68; 95% CI, 1.25-2.24). CONCLUSIONS: Inhaled sedation was associated with similar mortality and ventilation duration compared with intravenous sedation, while showing a shorter ICU stay and improved oxygenation. However, it is associated with a higher risk of AKI. Further large-scale multicenter trials are needed to validate these findings and refine the clinical role of inhaled sedation in ARDS.