Background: Postoperative sore throat (POST) is a common complication of endotracheal intubation. This study aimed to compare the efficacy of nebulization with ketamine or magnesium sulphate in reducing the incidence of POST. Methods: This comparative observational study included 88 patients undergoing elective surgery under general anesthesia. Patients were randomly divided into two groups: Group 1 received nebulization with 250mg of magnesium sulphate, while Group 2 received nebulization with 50mg of ketamine. Results: The incidence of POST was significantly lower in the ketamine group compared to the magnesium sulphate group at 4 and 6 hours postoperatively. Pain scores were also lower in the ketamine group at 4 and 6 hours. There were no significant differences in side effects between the two groups. Conclusion: Nebulization with ketamine is more effective than magnesium sulphate in reducing the incidence of POST and pain scores in patients undergoing elective surgery under general anesthesia with endotracheal intubation.