Introduction: Although intraoperative monitoring and control of cuff pressure are suggested to reduce the incidence of sore throat and other complications postoperatively, it is not routinely practiced by many anesthesiologists. In this study, we assessed the effect of patient positioning and pneumoperitoneum on endotracheal cuff pressure during laparoscopic surgeries with nitrous oxide (N₂O) anesthesia in the Trendelenburg position and reverse Trendelenburg position. Materials and methods: It was a prospective observational study on 96 patients scheduled for laparoscopic cholecystectomy (LAP CHOLE) and laparoscopic hysterectomy (TLH). Cuff pressure was measured at the time of first inflation of cuff up to 20–30 cm H₂O, and airway pressure was noted as zero reading. Cuff pressure was measured after 5 minutes subsequently, before pneumoperitoneum, 5 minutes after pneumoperitoneum, and at 15-minute intervals till desufflation and prior to extubation. Results: In our study, the increase in cuff pressure in the Trendelenburg position was 33.92 ± 4.32, 30.19 ± 3.07, and 31.10 ± 3.50, and in the reverse Trendelenburg position was 33.25 ± 3.82, 32 ± 6.45, and 30.81 ± 5.82 after 5, 15, and 30 minutes after the start of pneumoperitoneum, respectively. There was no significant difference between the two groups. The number of deflations was higher during the first 60 minutes for both groups. Our study showed a poor correlation between the airway pressures and ETT cuff pressures, contrary to previous studies. Conclusion: The use of N₂O increases the cuff pressure, and ETT cuff pressure continues to increase during the 1st hour of N₂O anesthesia. There is no correlation between airway pressures and endotracheal cuff pressure when the airway pressures are maintained within normal limits. So, regular monitoring of endotracheal tube (ETT) cuff pressure should be a part of the safe practice of anesthesia where N₂O is used.