A sore throat is the most frequent adverse side effect of general anesthesia. The purpose of this study was to compare the different types and timing of lidocaine application based on the effectiveness of reducing postoperative sore throat (POST) after endotracheal intubation. In group A, 8% lidocaine was sprayed on laryngopharyngeal structures immediately before intubation, and the distal ends of the endotracheal tubes (ETTs) were lubricated with 2% lidocaine gel. In group B, 8% lidocaine was sprayed, and ETTs were lubricated with normal saline. In groups C and D, no lidocaine was sprayed, and the ETTs were lubricated with normal saline (C, control) or with 2% lidocaine gel (D). In group E, 8% lidocaine was sprayed 10 min prior to endotracheal intubation, and the ETTs were lubricated with normal saline. In 527 patients, 28.2% reported POST at 24 h following extubation. Statistically significant differences in the incidence of POST were found only between group E (16.0%) and each of the other groups (28.4-38.5%), except for group B (26.5%). In conclusion, 8% lidocaine spray significantly reduced the incidence of POST if it was sprayed on laryngopharyngeal structures 10 min prior to endotracheal intubation.