Background: Postoperative sore throat (POST) is a common complication following general anesthesia with endotracheal intubation. This study compared the efficacy of 5% EMLA cream and betamethasone gel 0.05% applied on the endotracheal tube cuff in preventing POST.Methods: In this prospective, randomized study, 50 adult patients undergoing general anesthesia were allocated to receive either 5% EMLA cream (n=25) or betamethasone gel 0.05% (n=25) on the endotracheal tube cuff. The incidence and severity of POST, cough, and hoarseness of voice were assessed at 0, 6, and 24 hours post-extubation. Hemodynamic parameters and adverse events were also recorded.Results: The incidence of POST at 6 hours was significantly lower in the EMLA group (8%) compared to the betamethasone group (32%) (p=0.034). The severity of POST at 6 hours was also significantly lower in the EMLA group (0.1 ± 0.4) compared to the betamethasone group (0.4 ± 0.7) (p=0.048). The incidences of postoperative cough and hoarseness of voice were lower in the EMLA group at all time points, but the differences were not statistically significant (p>0.05). Hemodynamic parameters and adverse event profiles were comparable between the groups.Conclusion: The application of 5% EMLA cream on the endotracheal tube cuff significantly reduced the incidence and severity of POST at 6 hours compared to betamethasone gel 0.05% in adult patients undergoing general anesthesia. EMLA cream is an effective and safe alternative for preventing POST in this patient population.