OBJECTIVE The objective of this study was to evaluate the efficiency and response of gas exchange by the use of high frequency respiratory modalities in cases rescued after failure of conventional mechanical ventilation. METHODS A retrospective study of twelve premature infants that required high frequency ventilation (HFV) as rescue therapy for treatment of respiratory distress syndrome (RDS) because of failure of conventional mechanical ventilation (CNV) were studied. The mean weight and gestational age were 1,041 gr (500-1,730) and 28 weeks (26-34), respectively. Fifty percent of the infants weighed less than 1,000 grams. Two different respiratory apparatus were used. Five infants were treated using Infant Star and seven with Babylog 8000. The variables were analyzed by comparison of the means with significance taken as p < 0.05. RESULTS High frequency ventilation was initiated at 24 hours of life (2-86) and the mean duration was 33 hours (1-133). We saw a significant improvement in oxygenation after starting HFV and during the first and second controls after HFV initiation. PaO2 increased from 59 mmHg to 87 (HFV-initial), 119 mmHg (HFV-first control) and 98 mmHg (HFV second control; p < 0.05). Likewise, a/AO2 increased from 0.087 to 0.13 (HFV-initial), 0.19 (HFV-first control) and and 0.18 (HFV-second control; p < 0.05). The oxygenation index (OI) decreased from 23 to 16 (HFV-initial p < 0.05) and to 11 during the first and second controls (p < 0.01). Despite the improvement in oxygenation, there were no differences in mean airway pressure levels. We did not see any change in PaCO2 levels. The mortality rate was 58%, with a mean age at death of 82 hours of life (6-264). CONCLUSIONS High frequency ventilation might be used as a rescue therapy for treatment of respiratory distress syndrome since there is an improvement in oxygenation.