The objective of this observational cohort study at Georgetown University Hospital from January 1, 1994 through December 31, 1997 was to investigate race, Candida sepsis, and duration of oxygen exposure in infants with retinopathy of prematurity (ROP) with birth weight ≤1,000 g. The incidence of ROP was 70.8% (114/161). The incidence of stage III or greater ROP in the Caucasian infants was significantly higher at 46.7% (14/30) than in the African-American infants at 23.8% (20/84) with p < 0.02. In addition, the incidence of threshold disease was higher in Caucasian infants 33.3% (10/30) when compared to African-American infants 9.5% (8/84) with p < 0.002. Using multiple logistic regression, African-American race was found to be an independent protective factor against developing severe ROP [adjusted odds ratio 0.39; 95% confidence interval (UCI) 0.16–0.97]. Extremely-low-birth-weight African-American infants with comparable severity of illness (including birth weight, gestational age, duration of supplemental oxygen exposure, and Candida sepsis) are less likely to develop severe ROP than Caucasian infants.