BACKGROUND: Postoperative sore throat (POST) is a distressing complaint in adults after endotracheal intubation. This study aimed to evaluate the effect of topical application of a eutectic mixture of local anesthetics (EMLA) cream over the endotracheal tube (ETT) cuff on the incidence and severity of POST, cough, and hoarseness of voice in adults after surgery. METHODS: In this randomized, placebo-controlled study, adult patients 18 to 65 years old, in American Society of Anesthesiologists (ASA) physical status I and II, and of either sex were scheduled to receive 5% EMLA cream (intervention arm) or lubricant gel (placebo-controlled arm) applied over the ETT cuff. POST was graded as none (0), mild (1), moderate (2), or severe (3). A score of ≥2 was considered as significant POST. The incidence of POST at the sixth postoperative hour was the primary outcome. Secondary outcomes included the incidence of POST at 0, second, and 24 hours, and the incidence of significant POST (score ≥2). The incidence and severity of postoperative cough and hoarseness of voice were recorded simultaneously. RESULTS: Two hundred and four patients completed the study. The incidence of POST was significantly lower in the EMLA group versus placebo at the sixth postoperative hour (4.9% vs 40.1%; relative risk [RR], 0.12; 95% confidence interval [CI], 0.05-0.29; P < .001); and at 0 hour (74.5% vs 93.1%; RR, 0.8; 95% CI, 0.7-0.9; P < .001) and second hour (51.9% vs 84.3%; RR, 0.61; 95% CI, 0.5-0.75; P < .001) but comparable at 24 hours (1.9% vs 3.9%; RR, 0.5; 95% CI, 0.09-2.67; P = .4). The number needed to treat to prevent POST with EMLA cream application was 5 at 0 hour and 3 at the second and sixth hour. The proportion of patients with significant POST over 24 hours were less in the EMLA group (9.8% vs 43.1%; P < .001). The incidence of postoperative cough and hoarseness of voice was significantly less at the 0, second, and sixth hours in the EMLA group, but comparable at 24 hours. The incidence of severe cough (8.8% vs 31.4%; P < .001) and hoarseness of voice (2% vs 7.4%; P < .001) over 24 hours was less in the EMLA group. CONCLUSIONS: The application of EMLA cream over ETT cuff reduces the incidence and severity of POST, cough, and hoarseness of voice in adults after general anesthesia in the early postoperative period compared to lubricant gel.