We sought to determine the rate of spontaneous closure of the ductus arteriosus (DA) in very-low-birth-weight infants. This prospective observational study included 65 infants whose birth weight (BW) < 1500 g. Echocardiograms were done on day of life (DOL) 3 and 7, weekly for the first month, and bimonthly until ligation, discharge, or death. Treatment was reserved for infants with heart failure, acute renal impairment, or those with significant persistent or escalating respiratory support. Chi-square tests, Student T tests, and logistic regression models were used to identify possible associations between spontaneous ductal closure by DOL 7 and predictor variables. Patterns of spontaneous DA closure over time were examined using Kaplan-Meier survival analysis. The DA closed spontaneously in 49% infants by DOL 7. Rates of spontaneous closure by DOL 7 differed significantly by BW strata: 67% for BW > 1000 g, 31% for BW <or= 1000 g ( P < 0.01). Ninety-seven percent of infants > 1000 g did not require intervention, and the DA closed spontaneously prior to discharge in 94%. In a logistic regression model, only BW > 1000 g and male gender were significantly associated with spontaneous closure by 1 week of life. The median time to spontaneous closure differed significantly between infants in the two BW strata: 7 days for > 1000 g versus 56 days for <or= 1000 g ( P < 0.001). Intervention for the patent DA in infants > 1000 g BW is rarely indicated. In infants <or= 1000 g BW, deferring treatment decisions until at least 1 week of life may avoid unnecessary treatment exposure.