Many patients in the intensive care unit (ICU) depend on mechanical ventilation due to conditions such as severe lung disease, traumatic brain injury, or postoperative coma. While mechanical ventilation is a potentially life-saving intervention, it also has harmful side effects. Especially in patients with lung disease, such as the acute respiratory distress syndrome (ARDS), the lungs can have significantly different physiological and inflammatory characteristics, which differ across different lung regions. Inappropriate ventilator settings can result in cyclic opening and closing of collapsed alveoli and/or pulmonary overdistension, which, in turn, promotes secondary lung injury and inflammation, also referred to as ventilator-induced lung injury (VILI). Therefore, it is important to be able to adjust the ventilator settings to specific patient physiology and needs. Lung-protective ventilation strategies aim to mitigate VILI and involve small tidal volumes, low driving pressures, and respiratory rates resulting in low mechanical power, and adequate end-expiratory pressure while maintaining effective gas exchange. The primary focus of this thesis involves two physiological studies comparing the effects of a new flow-controlled ventilation (FCV) mode with pressure-controlled ventilation (PCV) in ICU patients. FCV, characterized by constant flow during both inspiration and expiration, holds promise for its potential lung-protective effects. The effects of FCV on lung physiology are assessed by using several advanced respiratory monitoring techniques, such as electrical impedance tomography and esophageal pressure measurements. The first study evaluates the effect of FCV versus conventional PCV on lung physiology in ICU patients who required postoperative mechanical ventilation following cardiothoracic surgery, a group characterized by relatively 'healthy' lungs. The second study is an ongoing study in ICU patients requiring mechanical ventilation for respiratory failure due to moderate to severe ARDS, for which preliminary results are presented.