Oxygen therapy is commonly administered to patients with acute cardiovascular conditions during hospitalisation. Both hypoxaemia and hyperoxia can cause harm, making it essential to maintain oxygen saturation (SpO2) within a target range. Traditionally, oxygen administration is manually controlled by nursing staff, guided by intermittent pulse oximetry readings. This study aimed to compare standard manual oxygen administration with automated oxygen administration (AOA) using the O2matic device. In this randomised controlled trial, 60 patients admitted to a cardiac department with an acute cardiovascular condition requiring oxygen therapy were randomised to either standard care (manual oxygen administration) or AOA via the O2matic device. The primary outcome was the percentage of time spent within the desired SpO2 range (92%-96% or 94%-98%) over 24 hours. Patients had a mean age of 75.8±12.4 years, with an average SpO2 of 93%. Those in the AOA group (n=25) spent significantly more time within the target SpO2 range (median 87.0% vs 60.6%, p<0.001) compared with the standard care group (n=28). Time spent below the desired SpO2 range was significantly lower in the AOA group (7.9% vs 33.6%, p<0.001). No significant differences in time spent above the desired SpO2 range were observed between the two groups. AOA with the O2matic device is superior to standard manual control in maintaining SpO2 within the target range in patients hospitalised with acute cardiovascular conditions. The automated systems significantly reduce the time spent in hypoxaemia without increasing hyperoxia. NCT05452863.