Post-operative sore throat (POST) is the consistent undesirable problem following general anesthesia. Various methods have been tried out to overcome the same. Many studies have proved ketamine to be one of the drugs in POST reduction. This study proposed to establish the efficacy of ketamine administered as gargle and nebulization in reducing the POST incidence in patients receiving general anesthesia with orotracheolaryngeal intubation. 100 adults were randomly assigned into two groups. Adults in group A (n=50) subjected to nebulization with ketamine 50 mg for 15 minutes and patients in group B (n=50) were subjected to gargle with ketamine 50 mg for 40 seconds. In both groups, all patients were intubated by an experienced anesthesiologist. After extubation, we assessed them for the occurrence and severity of POST at regular intervals. The POST incidence at the 0th, 1st, 2nd, 4th, 6th, 8th, 12th, and 24th hours was 14%, 12%, 24%, 42%, 40%, 24%, 16%, and 10% in ketamine nebulization group and 18%, 34%, 58%, 50%, 46%, 38%, 30%, and 16% in ketamine gargle group, respectively. The p-value at the 1st hr was statistically high with the occurrence of POST being lower in nebulization group. The overall occurrence with POST severity, both were lower in the ketamine nebulization compared to ketamine gargle group. Ketamine nebulization is an effective method for reducing POST than ketamine gargle, in the initial period after surgery.