Rationale: Baseline characteristics and management have changed over time in patients requiring mechanical ventilation; however, the impact of these changes on patient outcomes is unclear.

Objectives: To estimate whether mortality in mechanically ventilated patients has changed over time.

Methods: Prospective cohort studies conducted in 1998, 2004, and 2010, including patients receiving mechanical ventilation for more than 12 hours in a 1-month period, from 927 units in 40 countries. To examine effects over time on mortality in intensive care units, we performed generalized estimating equation models.

Measurements and Main Results: We included 18,302 patients. The reasons for initiating mechanical ventilation varied significantly among cohorts. Ventilatory management changed over time (P < 0.001), with increased use of noninvasive positive-pressure ventilation (5% in 1998 to 14% in 2010), a decrease in tidal volume (mean 8.8 ml/kg actual body weight [SD = 2.1] in 1998 to 6.9 ml/kg [SD = 1.9] in 2010), and an increase in applied positive end-expiratory pressure (mean 4.2 cm H₂O [SD = 3.8] in 1998 to 7.0 cm of H₂O [SD = 3.0] in 2010). Crude mortality in the intensive care unit decreased in 2010 compared with 1998 (28 versus 31%; odds ratio, 0.87; 95% confidence interval, 0.80–0.94), despite a similar complication rate. Hospital mortality decreased similarly. After adjusting for baseline and management variables, this difference remained significant (odds ratio, 0.78; 95% confidence interval, 0.67–0.92).

Conclusions: Patient characteristics and ventilation practices have changed over time, and outcomes of mechanically ventilated patients have improved.

Clinical trials registered with www.clinicaltrials.gov (NCT01093482).