Objective: To determine the relative risk of severe intraventricular hemorrhage (IVH) between two very early indomethacin treatment strategies. Study Design: Retrospective chart review <29 weeks gestation and <1350 g who received either indomethacin prophylaxis or very early echocardiography with indomethacin treatment only if the ductus arteriosus was patent. Results: A total of one hundred and two infants received prophylactic indomethacin (pINDO). Echochardiography was performed on 158 infants, whom 117 received indomethacin. Infants receiving pINDO had lower gestational age, but similar birth weight, gender, race, antenatal steroid exposure, delivery mode, Apgar scores, and need for resuscitation as infants evaluated by echocardiography. Grades III to IV IVH was observed less frequently in infants who received pINDO (OR 0.27, 95% CI 0.10 to 0.77, p = 0.014). Frequency of side effects and recurrent patent ductus arteriosus did not differ between treatment groups. Conclusion: pINDO reduces severe IVH when compared to an early echocardiography strategy.