INTRODUCTION: With the increased survival of very low birthweight (VLBW) infants, weighing less than 1500 g at birth, the incidence of retinopathy of prematurity (ROP), a significant cause of blindness among children in the United States, is also increasing. Preterm infants with a positive diagnosis of ROP during the perinatal period are at increased risk for ocular abnormalities and for deficits in visual function during later periods of development. Human milk has many antioxidant constituents including inositol, vitamin E, and beta-carotene that may protect against the development of ROP. OBJECTIVE: The objective of this study was to examine the effect of human milk feedings on the incidence of ROP among VLBW infants. STUDY DESIGN: Observational cohort study. PARTICIPANTS: We identified 283 VLBW infants admitted to the Georgetown University Medical Center Neonatal Intensive Care Unit (NICU) from January 1992 through September 1993. All infants surviving to receive enteral feeding and ophthalmologic examinations for ROP (n=174) were included in the analysis. METHODS: Type of feeding (human milk versus exclusive formula), presence of ROP, and potential confounding variables were abstracted retrospectively from medical records. ROP was present if any stage of ROP was diagnosed at any age during the initial NICU hospitalization; each case was counted once based on the worse severity of ROP in either eye. Multiple logistic regression was used to control for confounders. MAIN OUTCOME MEASURE: ROP. RESULTS: Major predictors of ROP were similar in both feeding groups including gestational age, days on mechanical ventilation, and total number of days on supplemental oxygen. The incidence of ROP differed significantly by type of feeding (human milk -41.0% vs. formula -63.5%, p=0.005). Human milk feeding independently correlated with a reduced odds of ROP (OR: 0.42, 95% CI: 0.19 to 0.93) (p=0.03), controlling for gestational age, duration of supplemental oxygen therapy, 5-minute Apgar score, and race. Human milk feeding independently correlated with a reduced odds of ROP (OR: 0.46, 95% CI: 0.18 to 0.91) (p=0.03), controlling for birthweight, duration of supplemental oxygen therapy, 5-minute Apgar score, and race. CONCLUSION: Human milk feeding among VLBW infants was associated with a lower incidence of ROP compared to exclusively formula-fed VLBW infants after adjusting for confounding variables.