Volutrauma resulting from large tidal volumes is one of the ventilator induced lung injury which contributes to chronic lung disease. Moreover, large tidal volumes lead to hypocapnea which results in reduced cerebral blood flow, periventricular leukomalacia and poor neurodevelopmental outcomes. Volume guarantee (VG) ventilation is a time-cycled, pressure-limited ventilation mode which targets a set expiratory volume of gas to be delivered to the patient with each inflation. Aim: To compare the effect of VG Versus Pressure Limited Ventilation on the outcome of preterm neonates with respiratory distress syndrome (RDS). Methods: This was a randomized clinical trial conducted on 96 preterm neonates whose gestational ages ranged from 30 weeks to 34 weeks who were diagnosed with RDS and received surfactant, they were randomly allocated to two groups. The first group received VG ventilation and the second group received pressure limited (PL) ventilation. Results: There were no statistically significant differences in neither the duration of mechanical ventilation nor the duration of oxygen requirement between the two studied groups, however there was a statistically significant shorter duration of post extubation CPAP in the VG group (P value 0.003). Neonates ≤ 32 weeks in the VG group had a shorter duration of CPAP and oxygen requirement than those ≤ 32 weeks in the PL subgroup with P value 0.003 and 0.043 respectively. They also had less incidence of hypocapnea (P value 0.002), and a trend to less IVH and hypercapnea in comparison to the other subgroup. Neonate >32 weeks in the VG had shorter duration of CPAP than those in the PL group with a P value of 0.002 whereas there was no significant difference in other complications or mortality. Conclusion: Post extubation CPAP period was significantly shorter in VG group. Shorter duration of CPAP and the whole duration on oxygen therapy in smaller premature neonates <32 weeks on VG mode.