Background: To observe and compare the efficacy and safety of dexmedetomidine administrated in two different modes in sedative and analgesic anesthesia. Methods: Sixty female patients, of American Society of Anesthesiologists physical status I or II, aged from 18-52 years and scheduled for elective plastic operations under sedative and analgesic anesthesia were randomly divided into a control group and an intervention group, with 30 patients in each group. All patients were administered IV midazolam 0.04mg/kg and a continuous infusion of 0.1 μg/kg/min of remifentanil at the beginning of anesthesia. Patients in the control group received IV dexmedetomidine (DEX) 1 μg/kg over 15 min followed by 0.4-0.7 μg/kg/h infusion while patients in the intervention group received IV DEX 1 μg/kg over 30 min followed by 0.4-0.7 μg/kg/h infusion. Heart rate (HR), mean arterial pressure (MAP), respiratory rate (RR), bispectral index (BIS) and Ramsay sedation scores (RSS) were recorded. The lowest respiratory rates (LRR), incidences of respiratory depression, incidences of oxygen supplementation by facial mask and thrusting the jaw, frequencies of body movements, and additional rescue drug administrations were also recorded. After surgery, recovery time, recall of intraoperative events, pain scores in postanesthesia care unit(PACU), and satisfaction of patients and surgeons were assessed. Results: The BIS at time points from 5 min after anesthesia to the end of surgery in the intervention group were significantly higher than those in the control group (P<0.05). The RSS scores at time points from 5 min after anesthesia to immediately after induction with DEX were significantly higher in the intervention group than those in the control group (P<0.05). The HR at time points from the beginning of surgery to 30 min after local anesthesia, the MAP at time points from 30 min after local anesthesia to the end of surgery, and the RR at time points from 5 min after anesthesia to the end of surgery were significantly higher in the intervention group than those in the control group (P<0.05). Compared with the control group, patients in the intervention group had higher LRR, lower incidences of respiratory depression, more oxygen supplementation by facial mask and thrusting the jaw, and a shorter recovery time (P<0.05). Conclusions: The two different dexmedetomidine administrations effectively sedated and provided analgesia for patients. Dexmedetomidine infused with a loading dose over 30 min had less impact on patients’ hemodynamics and respiration and could shorten the recovery time after anesthesia. Trial registration: Registered at the Chinese Clinical Trial Registry, registration number ChiCTR1900027958, date of registration: 07/12/2019.