Introduction: Laryngeal mask airway (LMA) are devices that facilitate oxygenation and ventilation without endotracheal intubation. During general anesthesia (GA), nitrous oxide (N₂O) can diffuse into the air-filled LMA cuff more rapidly than air. The increased cuff pressure may lead to malpositioning of the LMA, inadequate seal, ineffective ventilation, airway contamination, decreased mucosal capillary perfusion, and increased pharyngolaryngeal morbidity. The aim of this study was to compare cuff pressure changes and efficacy to maintain stable LMA intracuff pressures with air in one group and O₂ (oxygen):N₂O (50:50) mixture in the other and to study perioperative complications. Materials and methods: Study setting and design—a prospective randomized study conducted in a tertiary care institute. A total of 80 patients were divided into two groups, group I—LMA cuff inflated with air and group II—LMA cuff inflated with N₂O + O₂ mixture (50:50). Pressure gauge and transducer are attached to the pilot balloon using a three-way. LMA cuff pressure was monitored every 5 minutes for the first 15 minutes and then every 15 minutes for a duration of 2 hours. Postoperatively, patients were evaluated for complications like sore throat, dysphagia, and pharyngeal mucosal injury. Results: In group I—cuff pressure started rising from 5 minutes and reached 36.93 ± 5.75 at 10 minutes, whereas in group II, pressure recorded was 32.68 ± 3.12, with a p-value of 0.002 which is statistically significant. At 15 minutes, in group I, cuff pressures reached 41.15 ± 6.31; in group II, it reached 35.05 ± 3.65 (p-value of 0.05). Discussion: In this study, after evaluating and comparing the LMA cuff pressure variations with air and N₂O + O₂ mixture (50:50) during surgery, it can be concluded that continuous monitoring of cuff pressure and its maintenance within allowable limits is recommended. O₂: N₂O mixture provides a relatively stable cuff pressure in comparison to air during O₂:N₂O anesthesia.