Hypothesis: early use of HFO improves gazometry, survival and prevents chronic lung disease. Study design: randomized multicentric open study. Stratification according to birth weight. Patients: 170 newborn infants with RDS; 90 under HFO (OHF1, Dufour, France), BW 1400±542g, GA 29.8±2.8wks and 80 under CMV, BW 1342±519g, GA 29.7±2.7wks. Results: Need of surfactant (a/A < 0.2) was markedly reduced in the HFO group (30% versus 63%; p<0.05). Ventilatory failure led to 13 cross-over from CMV to HFO, 6 died, and 3 going from HFO to CMV, 3 died (p<0.05). No significant difference were found in the incidence of death (HFO=17%; CMV=20%), air leaks (24% vs 28%), patent ductus arteriosus(26% vs 32%), intracranial hemorrhage (any grade:29% vs 28%; grade 4:10% vs 18%), periventricular leukomalacia (3% vs 5%), retinopathy, extra oxygen supply at 28 days, mechanical ventilation at 28 days and chronic lung disease near term. 1 pulmonary hemorrhage was observed in HFO and 6 in CMV (p=0.052).Conclusions: rapid improvement in gas exchange under HFO was associated with an unchanged mortality and morbidity both short and long term. Different weaning strategies as well as restrictive use of surfactant could explain those findings and need further evaluations.