Clonidine in brachial plexus block prolongs analgesia of local anesthetics of short and intermediate duration. We performed a prospective randomized double-blinded study to determine the efficacy and adverse effects of clonidine mixed with a long-acting local anesthetic on postoperative analgesia. Sixty adult patients underwent elective rotator cuff repair using interscalene brachial plexus block combined with general anesthesia and were randomly divided into one of the following three groups. Placebo (n = 20): interscalene block with 40 mL of 0.5% bupivacaine with epinephrine (1/200000) and 1 mL of 0.9% saline, completed by 1 mL of 0.9% saline IM in the controlateral shoulder; Control (n = 20): interscalene block with 40 mL of 0.5% bupivacaine with epinephrine and 1 mL of 0. 9% saline, completed by 150 microg (=1 mL) of clonidine IM; Clonidine (n = 20): interscalene block with 40 mL of 0.5% bupivacaine with epinephrine and 150 microg (=1 mL) of clonidine, completed by 1 mL of 0.9% saline IM. During anesthesia hemodynamic variables and fractional expired isoflurane concentration (FeISO) were recorded. The following postoperative variables were assessed: duration of interscalene block, quality of pain relief on a visual analog scale, side effects, and consumption of morphine with a patient-controlled analgesia device over 48 h. Patient characteristics were comparable. During anesthesia mean arterial pressure, heart rate, and FeISO were significantly decreased in Clonidine and Control groups compared with Placebo group. Duration of analgesia, defined as the time elapsed from interscalene injection to the first morphine request, was 983 +/- 489 min in the Placebo, 909 +/- 160 min in the Control, and 829 +/- 159 min in the Clonidine groups. Pain scores and consumption of morphine at 24 h and 48 h showed no differences among the three groups. We conclude that adding 150 microg of clonidine in interscalene block does not prolong analgesia induced by 40 mL of bupivacaine 0.5% with epinephrine, but decreases mean arterial blood pressure and heart rate.