Dexmedetomidine is an α2-adrenergic receptor agonist that causes minimal respiratory depression compared with alternative drugs. This study investigated whether combined dexmedetomidine/fentanyl offered better sedation and analgesia than midazolam/fentanyl in dental surgery. Sixty patients scheduled for unilateral impacted tooth extraction were randomly assigned to receive either dexmedetomidine and fentanyl (D/F) or midazolam and fentanyl (M/F). Recorded variables were patient preoperative anxiety scores, vital signs, visual analogue scale (VAS) pain scores, Observer's Assessment of Alertness/Sedation Scale (OAAS) scores after drug administration, surgeon and patient degree of satisfaction, and the duration of analgesia after surgery. The OAAS scores were significantly lower for patients administered D/F compared to those who received M/F. The duration of analgesia after the surgical procedure was significantly longer in patients who received D/F (5.3h) than in those who received M/F (4.1h; P=0.017). The number of surgeons satisfied with the level of sedation/analgesia provided by D/F was significantly higher than for M/F (P=0.001). Therefore, dexmedetomidine/fentanyl appears to provide better sedation, stable haemodynamics, surgeon satisfaction, and postoperative analgesia than midazolam/fentanyl during office-based unilateral impacted tooth extraction.