Background: Acute kidney injury (AKI) is a frequent and serious complication after aortic surgery requiring cardiopulmonary bypass (CPB). Dexmedetomidine, a selective alpha-2 adrenoreceptor agonist, may reduce AKI because of its sympatholytic and anti-inflammatory effects against ischaemia-reperfusion injury. We investigated the effect of dexmedetomidine administration on AKI after aortic surgery requiring CPB in a placebo-controlled randomised controlled trial. Methods: A total of 108 patients were randomly assigned to an infusion of dexmedetomidine or saline at a rate of 0.4 mu g kg(-1)h(-1) for 24 h starting after anaesthetic induction. The primary outcome was the incidence of AKI, as defined by the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. The secondary outcomes included delirium and major morbidity. Safety outcomes were drug-related adverse events (bradycardia, hypotension). Results: AKI occurred in 7/54 (13%) subjects randomised to dexmedetomidine, compared with 17/54 (31%) subjects randomised to saline infusion (odds ratio=0.32; 95% confidence interval [CI], 0.12-0.86; P=0.026). Secondary outcomes, including stroke, mortality, and delirium, were similar between subjects randomised to dexmedetomidine (16/54 [30%] or saline control (22 [41%]; odds ratio=0.61 [95% CI, 0.28-1.36]). The incidence of bradycardia and hypotension was similar between groups (14/54 (26%) vs. 17/54 (32%) (odds ratio:0.76 (95%CI:0.33-1.76) and 29/54 (54%) vs. 36/54 (67%) (odds ratio:0.58 (95%CI:0.27-1.26), respectively). The length of hospital stay was shorter in the dexmedetomidine group (12 [10-17] days) vs saline control (15 [11-21] days; P=0.039). Conclusions: Pre-emptive dexmedetomidine administration for 24 h starting after induction of anaesthesia reduced the incidence of AKI after aortic surgery requiring CPB, without any untoward side-effects related to its sedative or sympatholytic effects.