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To describe the prevalence of hypocapnia and hypercapnia during the earliest period of mechanical ventilation, and determine the association between PaCO2 and mortality.Materials and Methods: A cohort study using an emergency department registry of mechanically ventilated patients. PaCO2 was categorized: hypocapnia (< 35 mm Hg), normocapnia (35–45 mm Hg), and hypercapnia (> 45 mm Hg). The primary outcome was survival to hospital discharge.A total of 1,491 patients were included. Hypocapnia occurred in 375 (25%) patients and hypercapnia in 569 (38%). Hypercapnia (85%) had higher survival rate compared to normocapnia (74%) and hypocapnia (66%), P < 0.001. PaCO2 was an independent predictor of survival to hospital discharge [hypocapnia (aOR 0.65 (95% confidence interval [CI] 0.48–0.89), normocapnia (reference category), hypercapnia (aOR 1.83 (95% CI 1.32–2.54)]. Over ascending ranges of PaCO2, there was a linear trend of increasing survival up to a PaCO2 range of 66–75 mm Hg, which had the strongest survival association, aOR 3.18 (95% CI 1.35–7.50).Hypocapnia and hypercapnia occurred frequently after initiation of mechanical ventilation. Higher PaCO2 levels were associated with increased survival. These data provide rationale for a trial examining the optimal PaCO2 in the critically ill.Hypocapnia and hypercapnia occur frequently after initiation of mechanical ventilation.Higher PaCO2 levels are associated with increased survival.Over ascending PaCO2, there is linear trend of increased survival up to PaCO2 of 66 - 75 mmHg, which has highest survival.