To determine whether the use of continuous transcutaneous oxygen monitoring (tcPO2) could reduce the incidence of retinopathy of prematurity (ROP) in pre-term infants receiving oxygen therapy, a randomized, prospective trial of constant monitoring using the transcutaneous oxygen monitor versus intermittent monitoring of oxygen was performed on a population of premature infants at very high risk for the development of ROP. Two hundred ninety-six infants were randomly assigned to either a constantly monitored (CM) or standard care (SC) group. CM infants had tcPO2 monitored continuously as long as they required supplemental oxygen, whereas SC infants had tcPO2 monitored only during the more acute state of their illness. Management of both groups was otherwise identical. One hundred one of 148 infants in the CM group and 113 of 148 in the SC group survived. The overall incidence of ROP was 51% in the CM group and 59% in the SC group (no significant difference). In infants over 1000 g birthweight, as the weight increased there was increasing risk of developing ROP in the SC group. The odds ratio for the ROPsc:ROPcm reached 7.6 in infants between 1200 and 1300 g in infants with Apgar scores greater than or equal to 8 at 5 minutes. The incidence of cicatricial ROP was similar in both groups: four in the CM and five in the SC group.