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Background Postoperative sore throat (POST) is commonly reported by patients after endotracheal intubation. This study was conducted to compare the efficacy of intravenous lidocaine and dexamethasone in the prevention of such problem. Patients and methods We included a total of 394 cases who were randomly divided using the closed-envelope method into two groups: group D that included 197 cases who received intravenous dexamethasone (8 mg), and group L that included the remaining 197 cases who received intravenous lidocaine (1.5 mg/kg). Both the incidence and risk factors for POST were assessed. Results Sore throat was reported by 115 (58.4%) cases in group L, whereas it was reported by 82 (41.6%) cases of cases in the other group. There was a marked reduction of sore-throat sensation in group D (P<0.001). Logistic regression revealed that the presence of blood on suction was a significant risk factor for developing sore throat after intubation. Conclusion Intravenous administration of dexamethasone appears to be more promising than lidocaine in decreasing the incidence of POST. [ABSTRACT FROM AUTHOR]