Introduction: Nasal continuous positive airway pressure (nCPAP) is one of the most commonly used non-invasive ventilation modes in neonates with transient tachypnea of the newborn (TTN). Non-invasive high frequency oscillatory ventilation (nHFOV) is an non-invasive ventilation mode that has been increasingly used in neonatal respiratory disorders. Based on the unique physiologic advantages that nHFOV offers, we hypothesized that nHFOV might result in a decrease in the duration of non-invasive positive pressure ventilation in neonates with TTN. Methods: Late preterm and term infants > 34 weeks’ gestation were included in the study. Infants were randomized into nHFOV or nCPAP groups. Treatment was started with standard settings in both groups. Infants who met treatment failure criteria were switched to nasal intermittent mandatory ventilation for further positive-pressure support. Results: Total of 60 infants were included in the study. Thirty of these infants were included in the nHFOV group and 30 were included in the nCPAP group. There was no difference between the groups in terms of duration of positive-pressure ventilation; however, it showed a decreasing trend in the nHFOV group (21 hours, IQR [16-68] vs 15 hours, IQR [11-33]; p=0.09). After adjusting for confounders, the nHFOV group had a shorter duration of positive-pressure ventilation compared with the nCPAP group (mean difference: 16.3 hours; 95% confidence interval [CI], 0.7 to 31.9; p=0.04). Conclusion: Non-invasive high frequency oscillatory ventilation can shorten the duration of positive-pressure ventilation and supplemental oxygen in TTN.