Experimental and clinical observational studies have shown potential benefits of statin administration in the acute respiratory distress syndrome (ARDS) by modulating inflammation and preventing worsening respiratory function. More recently, two randomized clinical trials failed to demonstrate an improved survival of ARDS patients treated with statins. In the first study, conducted by the ARDS Network, 745 patients with sepsis‑associated ARDS were randomized within 48-hours of onset to receive either rosuvastatin or placebo. There was no significant difference between the rosuvastatin and placebo groups for hospital mortality (primary outcome, 29% vs. 25%, P=0.21) or ventilator‑free days (15±11 vs. 15±11, respectively; P=0.96). In rosuvastatin‑treated patients, renal and hepatic failure free‑days were significantly lower than in the placebo group, raising serious safety concerns. In the second study (HARP-2 trial), 540 patients with ARDS were randomized within 48-hours of onset to receive either simvastatin (80 mg/day) or placebo. There was no significant difference between the study groups for number of ventilator‑free days (primary outcome, 13±10 in the simvastatin vs. 12±10 in the placebo group, P=0.21) or 28-day mortality (22% vs. 27%, respectively; P=0.23). No significant difference in serious adverse events was reported between groups. Herein, we discuss the main reasons for these negative findings and consider where there could be a role for statins in ARDS patients.