BACKGROUND: Several interventions have been investigated to prevent pain on intravenous injection of propofol. Clonidine as an alpha-2 agonist is recognized to be an effective analgesic. Therefore, oral premedication of clonidine has been explored in relation to pain responses to propofol injection. METHODS: In a randomized, double blind study, 82 ASA I-II patients were allocated to one of two groups: oral clonidine (2.5microgram/kg) 60 90 min before the induction with propofol and lidocaine 40 mg followed by intravenous propofol. The pain score in the groups was assessed as follows: 0 = no pain, 1 = minimal pain, 2 = moderate pain, 3 = severe pain. RESULTS: Nine patients in the lidocaine-pretreated group and 16 patients in the clonidine group experienced pain. In cases of injection site was in hand, the incidence of pain was 9/15 patients in the lidocaine group and 12/15 patients in the clonidine group, respectively; however, none/26 patients in the lidocaine group and 4/26 patients in the clonidine group in a forearm vein, respectively. There were no significant differences between the groups in terms of pain score regardless the injection sites. Oral clonidine also attenuated hemodynamic responses to a laryngoscopy and intubation. CONCLUSIONS: Oral premedication of clonidine 2.5microgram/kg revealed a comparable analgesic effect with intravenous lidocaine 40 mg on propofol-induced pain.