What is known about this topic • Automated oxygen control has been proven to increase time spent within SpO2 target range when compared with manual titration in cross-over studies lasting a maximum of 24 hours. • Algorithm choice may influence how successful titration will be, but comparisons of algorithms head-to-head are scarce. • A preterm infant’s response to an adjustment in FiO2 may change during the course of the admission as respiratory distress syndrome progresses. What this study adds • Automated oxygen titration by the OxyGenie algorithmwas associated with better oxygen saturation targeting during the entire admission while given oxygen when compared to titration by the CLiO2 algorithm. • This was accompanied by less time spent in hypoxia and hyperoxia for preterm infants supported by the OxyGenie algorithm. • Including episodes where no supplemental oxygen is administered reduces the effect size. How this study might affect research, practice or policy • Choice of automated oxygen controller is associated with how successful oxygenation targeting will be during the entire admission. • When researching a long period of oxygen titration focus should lie on phases of respiratory instability and/or when supplemental oxygen is administered.