BACKGROUND: Weaning from mechanical ventilation is a challenging phase of neonatal respiratory support [1]. Choosing efficient and safe noninvasive modality to prevent re-intubation and choosing the optimal time for weaning are key points for weaning success. The aim of the study is to compare the efficiency and safety of noninvasive high frequency oscillatory ventilation (NHFOV) versus noninvasive positive pressure ventilation (NIPPV) as respiratory support after extubation in preterms with respiratory distress syndrome (RDS). Also, the study compared the lung ultrasound findings between these 2 modalities and assessed the use of lung ultrasound score (LUS) as predictor for extubation outcome. METHODS: This study is a randomized controlled trial conducted on 60 preterm neonates with RDS. Patients were allocated into one of 2 groups: NIPPV or NHFOV as post-extubation noninvasive respiratory support. The 2 groups were compared regarding the incidence of extubation failure within 72 hours from extubation, oxygen needs, duration of application of the noninvasive modality, duration of admission, safety and mortality rate. LUS was assessed pre-extubation and 2 hours post-extubation. RESULTS: The study did not show a statistically significant difference in re-ventilation rate in NHFOV group (23.3%) compared to NIPPV group (30.0%), p = 0.56. Oxygen needs were significantly lower in NHFOV group compared to NIPPV groups (mean FiO2 31.8±6.09 vs 38±0.55, p = 0.007). The duration of the used noninvasive modality, CO2 concentration, LUS, and mortality rate showed statistically insignificant difference between both groups. There was a significant correlation between LUS and extubation outcome. CONCLUSION: NHFOV is a feasible noninvasive modality for respiratory support post-extubation in premature infants. LUS is a good predictor of extubation outcome in neonates.