To determine the efficacy of indomethacin to prevent the occurrence of symptomatic patent ductus arteriosus (PDA), a randomized clinical trial was conducted involving 32 preterm infants weighing 750 to 1500 g at birth who had hyaline membrane disease. By random assignment, 15 infants were given a single dose of indomethacin, 0.2 mg/kg intravenously, 24 hours after birth. Seventeen infants composed a control group for which indomethacin was reserved as treatment for symptomatic PDA. Birth weight, gestational age, male/female ratio, black/white ratio, and severity of disease were similar for both groups. Only one of the 14 survivors who received prophylactic indomethacin had symptomatic PDA, compared with nine of the 16 survivors in the control group (P = 0.007). There was no difference between the groups in development of bronchopulmonary dysplasia, duration of time endotracheal intubation, was required, duration in oxygen, duration to reach full feedings and regain birth weight, and duration of hospital stay. There was no difference between the two groups in incidence of intraventricular hemorrhage, and none developed necrotizing enterocolitis. These results indicate that the use of prophylactic indomethacin is beneficial in prevention of symptomatic PDA; the lack of differences in pulmonary sequelae or other complications may have been related to a population sample size not large enough to impart sufficient statistical power.