Provision of life support (mechanical ventilation) is required for most critically ill patients admitted to an intensive care unit (ICU). Delivery of oxygen to such patients often exposes them to abnormally high levels of oxygen. Humans are adapted to breathe air and it is plausible exposure to higher amounts of oxygen is harmful. We propose a definitive 40,000-participant randomised controlled trial to test the hypothesis that, compared with usual liberal oxygen therapy, conservative use of oxygen reduces mortality by 1.5 percentage points in adults who are mechanically ventilated in the ICU. This study combines clinical trial science with quality improvement so that participants will not only benefit from the study findings, but will also on average benefit from participation in the study itself. We consider this study will herald a new era in ICU research, providing a blue-print for future ICU research in New Zealand and internationally.