Background: The number of obese patients undergoing surgery, either bariatric or non-bariatric, is steadily increasing. These patients are more labile to the perioperative complications, such as hypoxemia, hypercapnia, and atelectasis. Intraoperative protective ventilation consisting of low tidal volume, high PEEP and recruitment maneuvers resulted in alveolar recruitment and optimization of intraoperative respiratory mechanics. Objective: This study tested two strategies of mechanical ventilation in obese patients during pneumoperitoneum to conclude which is better as regard gas exchange optimization and hemodynamic stability. Methods: Study was a randomized prospective comparative control study which was carried out on 50 obese patients with BMI 30-50 kg/m2. Patients were prepared for laparoscopic cholecystectomy. Patient's selection according to attendees at time of operation as a single numbers were protective ventilation (group A) and a double numbers were conventional ventilation (group B). Results: Study showed significance between oxygenation in both groups. Post-operative oxygenation in protective ventilation (group A). Mean Post P (A-a) O2 in group A was 27.93 (±7.76) mmHg, while in group B was 35.82 (±11.98) mmHg, p value (0.022).Hemodynamic instability observed in 24% in group A, but only occurred in 8% in group B. Conclusion: Study found that protective ventilation was superior to conventional ventilation as it was associated with better oxygenation in the post-operative in obese laparoscopic cholecystectomy. In spite of it was very effective in optimizing gas exchange, but associated with more hemodynamic affection.