Post-operative Sore Throat (POST), is unavoidable following endotracheal intubation. In our study, we compared the efficacy of 2% viscous lignocaine gargle over 5% ketamine gargle for the prevention of Post-operative Sore Throat (POST) in patients undergoing general anesthesia with endotracheal intubation. Methodology: 80 patients undergoing general anesthesia with endotracheal intubation were allocated into two groups lignocaine (Group L) and ketamine (Group K). Both the Groups were made to gargle five minutes with respective solutions before pre-medication. Group K were made to gargle 50 mg ketamine with 29 ml normal saline and in Group L gargling was done with 30 ml of 2% viscous lignocaine undiluted. The primary objective was to assess the incidence and severity of POST. Secondary objectives were, response to intubation every three minutes for initial 15 minutes, and cough in the post-operative period. Results: Incidence and severity of POST was signifiacantly high at the end of 2nd, 4th, 6th, 12th in Group L. (p = < .07) ( < .001) (< .001) (< .04). There was a significant increase in heart rate and mean arterial pressure in group at the end of 1st, 3rd and 6th minute after intubation in Group K. 4% in Group K and 12% in Group L had post-operative cough of Score 1.