The properties of dexmedetomidine (DEX) that result in titratable sedation and sympathetic modulation suggest that it would be suitable for use during carotid endarterectomy (CEA) performed under regional anesthesia. We performed a randomized, double-blind study in 56 patients having CEA under regional anesthesia and compared hemodynamic control using DEX versus a conventional sedation technique using midazolam and fentanyl standard (STD). Sedation was titrated to a Ramsay Sedation Score of 2-4 in both groups. The primary outcome was the number of pharmacological interventions required to treat deviations of arterial blood pressure and heart rate outside of predetermined limits. We also compared recovery hemodynamic profiles, patient satisfaction, and adverse cardiac and neurological events. There was no difference in the overall rate of hemodynamic interventions (DEX 80% versus STD 79%; P = 1.0). However, the nature of interventions differed in that patients in the DEX group were less likely to require treatment for hypertension and/or tachycardia (DEX 40% versus STD 72%; P = 0.03). The number of interventions per patient for hypertension and/or tachycardia was also lesser in the DEX group (P = 0.02). There were no significant differences in the numbers of patients needing intraoperative treatment for hypotension or bradycardia or in the need for intraarterial shunting. In the postanesthesia care unit, more patients in the DEX group required hemodynamic drug interventions (DEX 11, 44%, versus STD 4, 14%; P = 0.03). These were primarily for hypotension (DEX 7, 28% versus STD 3, 11%; P = 0.16). The number of patients requiring no additional pain relief in the postanesthesia care unit was significantly larger for patients in the DEX group (DEX 18, 72% versus STD 11, 38%; P = 0.027). DEX provides an acceptable alternative, without superiority to standard techniques for sedation during awake CEA.