Background: The main goal of mechanical ventilation is the maintenance of adequate oxygenation and ventilation. There is no guidelines on the mechanical ventilation in obese patients. This study aims to compare the effect of pressure controlled ventilation PCV vs. volume controlled ventilation VCV on oxygenation parameters in obese patients undergoing laparoscopic cholecystectomy. Methods: 70 obese patient of ASA physical status II, Body Mass Index of 30–40 kg/m2, scheduled for laparoscopic cholecystectomy were included in this prospective randomized study. All patients received VCV. Fifteen minutes after creation of pneumoperitoneum, they were randomized to receive either VCV (Group V) or PCV (Group P). The ventilatory parameters were adjusted accordingly to maintain the end‑ tidal CO2 between 30 and 40 mmHg. Primary outcome variable was mean airway pressures. Secondary outcomes were PO2/FiO2 ratio, dead space to tidal volume ratio and alveolar arterial oxygen tension gradient before and after creation of pneumoperitoneum. Results: Patients in group P showed a statistically significant (P < 0.05) higher level of PaO2/FiO2 ratio and mean airway pressure and lower value of PAO2–PaO2, dead space to tidal volume ratio and peak airway pressure than those in group V. Conclusion: PCV is a more efficient mode of ventilation in comparison with VCV mode regarding oxygenation in obese patients undergoing laparoscopic cholecystectomy.