Endotracheal intubation for general anesthesia causes postoperative sore throat (POST). This study is designed to evaluate the effect of high-dose remifentanil on the incidence of POST in patients after general anesthesia.Ninety-two patients scheduled for orthopedic lower extremity surgery under general anesthesia were randomly assigned into 1 of 2 groups. In the high-dose remifentanil (HR) group (n = 46), remifentanil was infused at a rate of 0.25 μg/kg/min and subsequently increased or decreased by 0.05 μg/kg/min per clinical demand. In the low-dose remifentanil (LR) group (n = 46), remifentanil was infused at a rate of 0.05 μg/kg/min. The incidence of POST was monitored at 0, 2, 4, and 24 hours postoperatively. Complications regarding opioids were compared between groups.The overall incidence of POST was higher in the HR group compared with that in the LR group [33 (72%) vs 18 (39%), P = .022]. The incidence of POST at 0, 2, and 24 hours after surgery was higher in the HR group compared with that in the LR group (P < .001, P = .001, and P = .001, respectively). The incidence of postoperative nausea, vomiting, drowsiness, and headache was similar between the groups. The incidence of postoperative shivering was higher in the HR group than in the LR group [10 (22%) vs 2 (4%), difference 17%, 95% CI 2%-33%, P = .027].A relatively large dose of intraoperative remifentanil increased the incidence of POST in patients for orthopedic surgery under general anesthesia.Clinicaltrials.gov Identifier: NCT03173339.