To establish the feasibility of a future large randomized trial to compare early treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) while awaiting spontaneous patent ductus arteriosus (PDA) closure. Preterm infants at <29 weeks of gestation with a PDA diameter >1.5 mm and <72 hours after birth were randomized to NSAIDs vs placebo. No open-label NSAID treatment was allowed in either arm, but all infants with PDA volume load received supportive management, including optimization of airway pressure, careful fluid management, and diuretics as needed. The pilot outcomes were recruitment rate and incidence of open-label treatment. Secondary clinical outcomes included chronic lung disease or death, the planned primary outcome for a future large trial. Overall, 54% of the approached parents consented to participate in the study. The median recruitment rate was 3 infants per month, and a total of 72 infants were randomized. One patient in each arm received open-label treatment. PDA closure rates were 74% for the NSAIDs arm vs 30% for the placebo arm, but this was not associated with significant changes in clinical outcomes. This pilot trial showed that recruitment of more than one-half of eligible infants with a low incidence of open-label treatment is feasible. PDA closure rates and clinical outcomes were similar to those reported in previous PDA trials. Copyright © 2020 Elsevier Inc. All rights reserved.