Rationale: Rationale: Baseline characteristics and management have changed over time in patients requiring mechanical ventilation, however the impact of these changes on patients' outcomes is unclear. Objective: 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 unit we performed a generalized estimating equation (GEE) 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 non-invasive positive pressure ventilation (5% in 1998 to 14% in 2010), a decrease in tidal volume [mean 8.8 ml/kg actual body weight (standard deviation 2.1) in 1998 to 6.9 ml/kg (standard deviation 1.9) in 2010], and an increase in applied positive end-expiratory pressure [mean 4.2 cm of water (standard deviation 3.8) in 1998 to 7.0 cm of water (standard deviation 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 to 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 to 0.92). Conclusions: Patient characteristics and ventilation practices have changed over time, and outcomes of mechanically ventilated patients have improved.