Assisted mechanical ventilation may alter the pressure profile in the thorax compared to normal breathing, which can affect the blood flow to and from the heart. Studies suggest that in patients with severe lung disease, airway pressure release ventilation (APRV) may be haemodynamically beneficial compared to other ventilator settings. The primary aim of this study was to investigate if APRV affects cardiac index in intubated intensive care patients without severe lung disease when compared to pressure support ventilation (PSV). The secondary aim comprised potential changes in other haemodynamic and ventilatory parameters. Twenty patients were enrolled in the intensive care unit (ICU) at Sahlgrenska University Hospital. Eligible patients met the inclusion criteria; 18 years of age or above, intubated and mechanically ventilated, triggering and stable on PSV mode, with indwelling haemodynamic monitoring via a pulse-induced continuous cardiac output (PiCCO) catheter. The study protocol started with a 30-min interval on PSV mode, followed by a 30-min interval on APRV mode, and finally a 30-min interval back on PSV mode. At the end of each interval, PiCCO outputs, ventilator outputs, arterial and venous blood gas analyses, heart rate and central venous pressure were recorded and compared between modes. There was no significant difference in cardiac index (3.42 vs. 3.39 L/min/m ) between PSV and APRV, but a significant increase in central venous pressure (+1.0 mmHg, p = .027). Furthermore, we found a significant reduction in peak airway pressure (-3.16 cmH O, p < .01) and an increase in mean airway pressure (+2.1 cmH O, p < .01). No statistically significant change was found in oxygenation index (partial pressure of O pO /fraction of inspired oxygen) nor in other secondary outcomes when comparing PSV and APRV. There was no significant association between global end-diastolic volume index and cardiac index (R  = 0.0089) or central venous pressure (R  = 0.278). All parameters returned to baseline after switching the ventilator mode back to PSV. We could not detect any changes in cardiac index in ICU patients without severe lung disease during APRV compared to PSV mode, despite lower peak airway pressure and increased mean airway pressure.