PURPOSE: Anxiolytic and possible side effects of clonidine 150 μg compared to midazolam 7.5 mg for premedication in surgical wisdom tooth extraction were evaluated. METHODS: In a prospective, randomized, double-blind crossover trial, ten patients undergoing bilateral wisdom tooth surgery received clonidine or midazolam orally 1 h before the treatment. Patients receiving midazolam for the first surgery received clonidine at the second surgery and vice versa. The anxiolytic efficacy was evaluated with a visual analogue scale (VAS) upon admission and 30, 50 and 60 min after administration of the medication. Patient satisfaction was recorded on a VAS after surgery and 7 days postoperatively. RESULTS: As soon as 30 min after administration of midazolam (p < 0.03) and clonidine (p < 0.02), an anxiolytic effect was recorded. Both medications did not differ in patient satisfaction. CONCLUSION: Oral administration of clonidine 150 μg and midazolam 7.5 mg were rated as medications with equal anxiolytic effects before wisdom tooth surgery under local anesthesia.