Mechanical ventilation can be a life–saving intervention in critically ill patients with acute respiratory failure and guarantees gas exchange in patients under general anesthesia for surgery. Over the recent years we have learned that mechanical ventilation can also cause injuries to the lung. These findings caused a paradigm shift towards lung–protective ventilation strategies including the use of low tidal volume (VT), an appropriate level of positive end-expiratory pressure (PEEP), and a low driving pressure (ΔP). In the first of this thesis, we focused on lung protective ventilation strategies in critically ill patients. We describe the use of a low VT in invasively ventilated patients with acute respiratory distress syndrome due to COVID–19 and reveal its association with relevant clinical outcomes. Furthermore, we present results from a clinical study in patients after cardiac surgery receiving postoperative ventilation using a fully automated closed–loop modus of ventilation. The second part of this thesis lays focus on lung protective ventilation strategies in the setting of intraoperative ventilation in the operating room. We describe astounding sex differences in use of tidal volume during surgery. Ultimately, we present the protocol and an interim analysis of an international multicenter randomized clinical study comparing a personalized high PEEP – aiming to keep ΔP low– strategy versus a standard PEEP strategy in patients receiving open abdominal surgery.