BACKGROUND: The Pragmatic Randomized Optimal Platelet and Plasma Ratios (PROPPR) study evaluated the effects of plasma and platelets on hemostasis and mortality after hemorrhage. The pulmonary consequences of resuscitation strategies that mimic whole blood, remain unknown. METHODS: A secondary analysis of the PROPPR study was performed. Injured patients predicted to receive a massive transfusion were randomized to 1:1:1 versus 1:1:2 plasma-platelet-red blood cell ratios at 12 Level I North American trauma centers. Patients with survival >24 h, an intensive care unit (ICU) stay, and a recorded PaO2/FiO2 (P/F) ratio were included. Acute respiratory distress syndrome (ARDS) was defined as a P/F ratio < 200, with bilateral pulmonary infiltrates, and adjudicated by investigators. RESULTS: Four hundred fifty-four patients were reviewed (230 received 1:1:1, 224 1:1:2). Age, sex, injury mechanism, and regional abbreviated injury scale (AIS) scores did not differ between cohorts. Tidal volume, positive end-expiratory pressure, and lowest P/F ratio did not differ. No significant differences in ARDS rates (14.8% vs. 18.4%), ventilator-free (24 vs. 24) or ICU-free days (17.5 vs. 18), hospital length of stay (22 days vs. 18 days), or 30-day mortality were found (28% vs. 28%). ARDS was associated with blunt injury (OR 3.61 [1.53-8.81] P < 0.01) and increasing chest AIS (OR 1.40 [1.15-1.71] P < 0.01). Each 500 mL of crystalloid infused during hours 0 to 6 was associated with a 9% increase in the rate of ARDS (OR 1.09 [1.04-1.14] P < 0.01). Blood given at 0 to 6 or 7 to 24 h were not risk factors for lung injury. CONCLUSION: Acute crystalloid exposure, but not blood products, is a potentially modifiable risk factor for the prevention of ARDS following hemorrhage.