Although the mechanism of tourniquet-induced hypertension is still unclear, plasma norepinephrine concentrations continuously increase in parallel to arterial blood pressure during tourniquet inflation. Clonidine attenuates hyperadrenergic and hyperdynamic responses. We investigated the effects of clonidine on prolonged tourniquet inflation. Twenty-nine patients scheduled for elective orthopedic surgery were randomly assigned to receive IV clonidine (3 μg/kg;n = 14) or placebo (n = 15) before tourniquet inflation of the lower limbs under general anesthesia in a double-blinded manner. Arterial blood pressure, heart rate, epinephrine, and norepinephrine plasma concentrations were measured before tourniquet inflation, 60 min after tourniquet inflation, just before tourniquet deflation, and 20 min after tourniquet deflation. Mean arterial blood pressure and norepinephrine plasma-concentrations were significantly lower in the Clonidine group compared with Control after 60 min tourniquet inflation (P = 0.016;P = 0.006). Immediately before deflation of the tourniquet, the difference for mean arterial pressure between groups was even more pronounced (P = 0.005). Twenty minutes after deflation mean arterial blood pressure in the Control group was still increased and significantly higher compared with the Clonidine group (P = 0.002). In conclusion, preoperative IV clonidine blunts hyperadrenergic and hyperdynamic responses resulting from prolonged tourniquet inflation under general anesthesia in ASA class I–II patients.