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To investigate whether early treatment with inhaled nitric oxide (iNO) could prevent bronchopulmonary dysplasia (BPD) in very preterm infants.A non-randomized, controlled trial was conducted prospectively in 27 neonatal intensive care units over 12 months. Preterm infants with gestational age < 34 weeks and after 7 days of life, who received invasive mechanical ventilation (MV) or nasal continuous positive airway pressure for > 2 days, were treated either with low-dose iNO (from 5 as initial dose to 2 parts per million as maintenance dose for ≥7 days, n = 162) or as non-placebo control (n = 240). Primary outcome was the incidence of moderate-to-severe BPD at 36 weeks postmenstrual age and/or death before discharge. Secondary outcomes were major complications.iNO was started on average on day 19 of life (median duration 18 days, range 7 to 55 days). Rate of survival without BPD was significantly lower in the iNO than in the control group, whereas overall rates of BPD, death and major complications were similar between the two groups. Infants who started MV and iNO on postnatal days 15 to 21 had significantly increased survival without BPD (47.6% vs 17.1%, P = 0.03, relative risk 2.7, 95% confidence interval 1.1 to 6.5). Additionally, pooled data from both groups showed that rates of perinatal co-morbidities and postnatal complications were higher in BPD infants than in non-BPD infants. The overall incidence of BPD was 55.6% and 75.9% for birth weight < 1500 and < 1000 g, respectively, or 1.6% for the total population < 34 weeks of gestation admitted through the network.Treatment with low-dose iNO did not decrease the overall risk of BPD and death nor showed adverse effects in short-term morbidities among very preterm infants. The benefit of delayed iNO treatment on BPD warrants further studies.