The aim of this prospective randomized study is to compare the outcomes of the early use of either high frequency oscillation (HFO) or conventional mechanical ventilation (CMV) in patients with pediatric acute respiratory distress syndrome (PARDS). We allocated two hundred PARDS patients over 5 years in 1:1 ratio to either mode. The HFO group showed a significantly higher median partial arterial oxygen pressure to fraction of inspired oxygen (PaO2/FiO2) values after 24 hours of enrollment (p=0.011), higher oxygenation index (OI) decrease percent (p=0.004) and lower cross-over rates (p<0.001), whereas no differences in 30-day mortality, length of stay (LOS) or ventilation days (p=0.77, p=0.28, p=0.65 respectively). The second day values (after 24 hours) of both OI and PaO₂/FiO₂ were found to be more significant discriminators for mortality when compared to the baseline values (cutoff values >8.5, ≤139 respectively). PARDS patients with baseline OI> 16 had a better chance of survival if initially ventilated with the HFO (p=0.004). Although the HFO mode appeared to be a safe mode with a significant better oxygenation improvement (after the first 24 hours) and fewer cross-over rates, it failed to show differences as regards mortality or LOS when compared to the CMV adopting protective lung strategy. In PARDS, HFO had a superior advantage in improving oxygenation, yet with no significant mortality improvement, as multi-organ dysfunction syndrome (MODS) was the most common cause of death in our study and not refractory hypoxemia which is the main problem in PARDS; highlighting that mortality in PARDS is multi-factorial and may not depend only on how fast oxygenation improves. Keywords : conventional mechanical ventilation, randomized, high frequency oscillation, pediatric acute respiratory distress syndrome, outcome