OBJECTIVE Conflicting data exist on the effect of dexmedetomidine on delirium. For the present study, a randomized trial was performed to investigate the effect of perioperative dexmedetomidine on the rate of postoperative delirium after cardiac surgery. METHODS A randomized controlled trial. METHODS University hospital. METHODS Patients (n = 169) undergoing elective cardiac surgery (coronary artery bypass graft surgery, valve surgery, or combined surgery) with cardiopulmonary bypass. METHODS Patients received a sevoflurane-based general anesthesia and were randomly assigned 1:1 to receive a dexmedetomidine infusion that started in the operating room (0.7 μg/kg/h) and continued into the intensive care unit (0.4 μg/kg/h) or an equivolume infusion of placebo. RESULTS A decrease in the rate of delirium in the dexmedetomidine group compared with the placebo group was demonstrated (6 of 84 [7.1%] v 16 of 85 [18.8%]; p = 0.02; odds ratio [OR] 0.33 [95% confidence interval {CI} 0.12-0.90]). Reduced intensive care unit and hospital lengths of stay also were observed (18 [18-22] hours v 22 [18-39] hours; p = 0.002 and 17 [7-20] days v 19 [8-21] days; p = 0.04, respectively). Mortality at 30 days was 2 (2.4%) in both groups. On multivariate analysis, only dexmedetomidine administration (OR 0.24 [95% CI 0.08-0.74]) and cardiopulmonary bypass time (OR 1.02 [95% CI 1.01-1.03] for increases of 1 min) were independent predictors of delirium development. CONCLUSIONS Dexmedetomidine administered during and after general anesthesia for cardiac surgery with cardiopulmonary bypass decreased the rate of postoperative delirium and intensive care unit and hospital lengths of stay.