Objective To investigate the effect of dexmedetomidine (DEX) combined with remifentanil on hemodynamic changes, clinical anesthesia efficacy and postoperative comfort in patients undergoing thyroid surgery. Methods Fifty patients undergoing thyroid surgery under general anesthesia in Third Affiliated Hospital of Jinzhou Medical University from December 2018 to April 2019 were recruited in this study. They were randomly divided into DEX group (DEX+remifentanil, n=25) and propofol group (propofol+remifentanil, n=25). The systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), and blood oxygen saturation (SPO₂) were recorded at the time of entry (T0), intubation (T1), skin incision (T2), beginning (T3) and end of operation (T4), eye opening (T5), extubation (T6), and leaving the post-anesthesia care unit (PACU, T7). The score of observer′s assessment of alertness/sedation scale (OAA/S), time to PACU Aldrate score more than 9 points, and Steward recovery score at T5, T6, time of orientation recovery and 10min after extubation, and the score of visual analog scale (VAS) on the first day post-operatively were investigated and recorded. The adverse reactions after extubation were observed. SPSS statistics 21.0 was used for data analysis. According to different data type, t test or χ² test was used for data comparison between two groups. Results No intraoperative awareness was observed among the 50 patients. There were significant differences in SBP, DBP, and HR from T2 to T7 (P<0.05), and in SPO₂ at T5 and T7 in the 2 groups (P<0.05). DEX group had obviously shorter T5 [(1.08±0.81) vs (6.56±1.87)min], T6 [(2.04±1.10) vs (8.48±1.81)min], time of orientation recovery [(1.56±0.87) vs (10.32±2.93)min], time to PACU Aldrate score more than 9 points [(5.28±1.10) vs (12.48±4.44)min], statistically less cases of restlessness (0 vs 3 cases), cough (2 vs 11 cases), respiratory depression (0 vs 10 cases), remarkably lower scores of OAA/S [(1.12±0.33) vs (2.12±0.67)] and VAS[(5.20±0.77) vs (2.72±1.10)], and notably higher score of awareness [(4.12±0.73) vs (5.80±0.41)] when compared with propofol group(all P<0.05). Conclusion Compared with propofol treatment, DEX treatment causes more stable hemodynamics during anesthesia maintenance, and has better advantages in improvement of the quality of recovery.