Mechanical ventilation is an often–needed and sometimes even life–saving intervention in critically ill patients, but has a strong potential to harm the lung. Lung–protective ventilation could prevent ventilator–induced lung injury (VILI), but its use has challenges. Lung–protective ventilation includes the use of a low tidal volume (VT) and a low driving pressure (ΔP), which is a measure for VT in relation to the respiratory system compliance (CRS). One recent ventilation parameter that receives increasing attention is the mechanical power of ventilation (MP). MP is a summary variable and reflects the amount of energy used to ventilate a patient and the substantial dissipation of energy during invasive ventilation, probably resulting in ‘heat’ or inflammation and therefore potentially leading to VILI. MP has associations with outcome in patients with and without acute respiratory distress syndrome (ARDS). With so many ventilation variables that must be adjusted to achieve lung–protective ventilation, with opposite or non–intuitive effects on MP, it could be difficult to set the ventilator correctly. This could be solved by introducing ‘automated’ or ‘closed–loop’ ventilation modes. One sophisticated mode of closed–loop ventilation is INTELLiVENT–Adaptive Support Ventilation (ASV). This thesis contains studies of closed–loop ventilation and the mechanical power of ventilation (MP). The first part focuses on practical aspects of use of closed–loop ventilation, the second part compares closed–loop ventilation with conventional ventilation with regard to key ventilation parameters and MP and the third part explores which ventilation parameters are needed to prioritize when targeting a low MP