Background: Meconium aspiration syndrome (MAS) is one of the most common causes of severe respiratory failure in infants born at term or post-term gestation. Aim and objectives: To assess continuous positive airway pressure versus conventional mechanical ventilation in management of neonatal meconium aspiration syndrome. Patient and methods: This Prospective randomized controlled trial conducted on fifty newborns admitted to NICU of Benha university hospitals and Benha Insurance hospital with meconium aspiration syndrome (MAS). They divided into two groups: Group 1: 25 cases were treated by conventional mechanical ventilation (CMV) and Group 2: 25 cases were treated by Continuous Positive Airway pressure (CPAP). Results: There was no statistically significant difference between the studied groups as regard maternal age. There was statistically significant increase for mechanical ventilation needing in group 2 compared to group 1. There was high statistically significant increase in total oxygen duration in group 1 compared to group 2. There was statistically significant difference between the studied groups as regard hospital stay. No parameter was associated with pulmonary hypertension in patients. Conclusion: Compared to conventional mechanical ventilation, our study produced evidence that CPAP in neonates with MAS reduces the subsequent need for MV, oxygen duration, hospital stay and incidence of sepsis with no significant correlation between total oxygen duration and maternal age, gestational age at delivery, Apgar 1 or 5.