Retinopathy of prematurity (ROP) is a potentially blinding disease of preterm infants. 21 days of computer-recorded transcutaneous oxygen (TcPO2) data were compared in 31 infants with stage 3 or greater ROP and 38 infants with no ROP or stage 1 or 2. In a multiple logistic regression adjusted for significant perinatal factors (birthweight, gestation, and intraventricular haemorrhage), babies with stage 3 or higher ROP showed an increased variability of TcPO2 in week 1 (p < 0.01) and 2 (p = 0.012) but not week 3. Variability of TcPO2 in the first 2 weeks of life is a significant predictor of severe ROP.