Background For patients undergoing endoscopic sinus surgery, intranasal injection of epinephrine can cause acute increases in heart rate and blood pressure. Objective Among the drugs for reducing hyperdynamic effects, dexmedetomidine and remifentanil are expected to blunt the acute hemodynamic responses after intranasal injection of epinephrine. Our study compared a difference in the 2 drugs in their abilities to blunt the hemodynamic responses in intraoperative period and postoperative profile. Methods In this study, the patients were randomly divided into the dexmedetomidine and remifentanil groups. During the intraoperative period, the hemodynamic values were recorded. The surgical condition was assessed by a single surgeon. During the postoperative period, hemodynamic values, sedation scale score, and pain score were recorded. Result No significant differences in hemodynamic variables were found between the groups before and after intranasal injection of epinephrine. Comparison of the group mean values before endotracheal intubation revealed that the blood pressure values in the remifentanil group were significantly lower than those in the dexmedetomidine group. At 2 minutes after endotracheal intubation, blood pressure and heart rate values in the remifentanil group were significantly lower than those in the dexmedetomidine group. The sedation score was significantly lower in the dexmedetomidine group on arrival and at 30 minutes after arrival at the postanesthetic care unit ( P < .001 and P = .001, respectively). At 30 and 60 minutes after the operation, the pain scores were significantly lower in the dexmedetomidine group ( P = .015 and P = .001, respectively). Conclusion Dexmedetomidine had better postoperative sedative and analgesic effects than remifentanil for patients undergoing endoscopic sinus surgery in this study. Remifentanil and dexmedetomidine attenuated acute hemodynamic responses to be within normal ranges after intranasal injection of epinephrine, and no significant differences in terms of hemodynamic variables. Remifentanil was superior to dexmedetomidine in inducing hypotension during endotracheal intubation.