Surfactant therapy in hyaline membrane disease (HMD) does not suppress all risks of subsequent broncho-pulmonary dysplasia. This study aimed to estimate the efficacy of Surfexo followed by high frequency ventilation (HFV) on respiratory parameters and long term outcome. 47 neonates (44 premature) with HMD received first Surfexo then HFV whenever hypercarbia (pH < 7.25, PaCO2 > 7 kPa) and/or hypoxaemia (PaO2 < 7kPa, FiO2 = 0.5) continued. Surfactant was given at 3 hours of life (mean), HFV was started at 5 h (mean) and continued for 36 h (mean). FiO2 was lowered after a HFV of 3 h (p < 0.01) and mean broncho-tracheal pressure decreased after 12 h (p < 0.001). Six children deceased (1 from massive pulmonary haemorrhage, 5 from neurological complications), 1 developed pneumothorax (this was the only barotraumatic complication in our series), 2 children had a mild broncho-pulmonary dysplasia. All the 38 remaining patients had a good uncomplicated outcome. Thus Surfexo -HFV association appears to be an excellent therapy of HMD in newborns.