Invasive mechanical ventilation is often initiated in the ED, and mechanically ventilated patients may be kept in the ED for hours before ICU transfer. Although lung-protective ventilation is beneficial, particularly in ARDS, it remains uncertain how often lung-protective tidal volumes are used in the ED, and whether lung-protective ventilation in this setting impacts patient outcomes. What is the association between the use of lung-protective ventilation in the ED and outcomes among invasively ventilated patients? A retrospective analysis (2011-2017) of a prospective registry from eight EDs enrolling consecutive adult patients (≥ 18 years) who received invasive mechanical ventilation in the ED was performed. Lung-protective ventilation was defined by use of tidal volumes ≤ 8 mL/kg predicted body weight. The primary outcome was hospital mortality. Secondary outcomes included development of ARDS, hospital length of stay, and total hospital costs. The study included 4,174 patients, of whom 2,437 (58.4%) received lung-protective ventilation in the ED. Use of lung-protective ventilation was associated with decreased odds of hospital death (adjusted OR aOR, 0.91; 95% CI, 0.84-0.96) and development of ARDS (aOR, 0.87; 95% CI, 0.81-0.92). Patients who received lung-protective ventilation in the ED had shorter median duration of mechanical ventilation (4 vs 5 days; P < 0.01), shorter median hospital length of stay (11 vs 14 days; P < .001), and reduced total hospital costs (Can$44,348 vs Can$52,484 US$34,153 vs US$40,418; P = .03) compared with patients who received higher tidal volumes. Use of lung-protective ventilation in the ED was associated with important patient- and system-centered outcomes, including lower hospital mortality, decreased incidence of ARDS, lower hospital length of stay, and decreased total costs. Protocol development promoting the regular use of lung-protective ventilation in the ED may be of value.