Remifentanil target-controlled infusion and dexmedetomidine single-dose administration are known to reduce airway response and hemodynamic stimulation during anesthetic recovery. We compared the effects of 2 drugs on the prevention of cough during emergence. We enrolled 70 female patients aged 20-60 years with American Society of Anesthesiologists (ASA) I-II who underwent general anesthesia for elective thyroidectomy. The patients were randomly assigned to remifentanil (group R) or dexmedetomidine (group D). Anesthesia was maintained with sevoflurane and effect-site target-controlled infusion of remifentanil. In group D, remifentanil was discontinued, and dexmedetomidine 0.5 μg/kg was given 10 minutes before the end of surgery. In group R, remifentanil target-controlled infusion at an effective-site concentration of 2.0 ng/mL was maintained during emergence until extubation. The cough grade, hemodynamic values, respiration, and other recovery profiles were evaluated during the periextubation period. The proportion of patients with no cough or just a single cough during extubation was significantly higher in group R than in group D (96.8% vs. 55.9%). The change of mean arterial pressure and heart rate were not significantly different during extubation in both groups. Respiratory rate and the incidence of residual sedation after extubation were lower in group R. There were no desaturation events and no differences in time to extubation or duration of postanesthesia care unit stay in both groups. Remifentanil target-controlled infusion reduces emergence cough from general anesthesia more effectively than single-dose dexmedetomidine. However, a single-dose of dexmedetomidine has the effect with respect to respiratory and hemodynamic stability during emergence.