Abstract. AIM: The aim of our study was to quantify arterial carbon dioxide levels (PaCO2) achieved by ventilating extremely preterm neonates in volume guarantee mode targeting tidal volumes of approximately 4 ml/kg. METHODS: We performed a prospective trial on preterm infants with gestational age ≤28 weeks, birth-weight ≤1000 grams, postnatal age <48 hours and are supported by mechanical ventilation. All infants were ventilated using volume guarantee plus synchronized intermittent positive pressure ventilation (SIPPV + VG mode). Primary outcome was the average first PaCO2 in neonates and number of these infants with unacceptable first PaCO2. Pre-specified secondary outcomes were the average PaCO2 in infants ventilated during the first 48 hrs of ventilation and number of blood gases with an unacceptable PaCO2 in the first 48 hours. Sixty two infants were enrolled and 218 blood gases recorded up to 48 hours of age. RESULTS: The mean PaCO2 on the first arterial blood gas for infants ventilated in VG mode from admission to the nursery was 39.5 ± 6.3. The mean PaCO2 in the first 48 hours was 39.37 ± 6.99 mmHg. In our study, 91% of all PaCO2 values in the first 48 hours were between 35 and 60 mmHg. PaCO2 levels were in the acceptable range in 93% of infants at the time of first ABG measurement and in 91% of blood gases during the first 48 hours of ventilation. CONCLUSION: Newborn infants ventilated with volume guarantee ventilation targeting approximately 4 ml/kg of tidal volume, have acceptable PaCO2 levels at the first blood gas measurement and during the first 48 hours of ventilation.