Background: Post-operative sore throat (POST) is a common complication following tracheal intubation during surgeries, contributing to patient discomfort and dissatisfaction. Ketamine, a noncompetitive N-methyl-D-aspartate receptor antagonist, has demonstrated potential in mitigating POST. Aim and Objective: This clinical study evaluated the efficacy of ketamine nebulization in reducing POST in patients undergoing elective surgeries. Materials and Methods: A prospective, randomized, double-blinded, comparative, clinical study with a sample size of 60 patients was conducted at RKDF Medical College, Hospital, and Research Centre, Bhopal, over one year. Patients were divided into the ketamine nebulization group (n =30) and the control group (n = 30). POST severity was assessed using a standardized scoring system, and secondary outcomes, including analgesic consumption and patient satisfaction, were evaluated. Results: In the ketamine nebulization group, 83.3% of patients experienced no sore throat, while 86.7% of the control group reported post-operative sore throat (POST). The severity of POST, as measured by mean scores, was significantly lower in the ketamine nebulization group compared to the control group. Analgesic consumption in the ketamine nebulization group was notably reduced in the post-anesthesia care unit (PACU) and at 24 hours postoperatively. Patient satisfaction scores, evaluated using a visual analog scale (VAS), were significantly higher in the ketamine nebulization group compared to the control group. Conclusion: Ketamine nebulization effectively reduces POST and improves peri-operative outcomes in patients undergoing elective surgeries. This adjunctive therapy holds promise for enhancing post-operative care and patient experience.