ABSTRACT: Cardiac surgery is associated with a high risk of cardiovascular and other complications that translate into increased mortality and healthcare costs. This retrospective study was designed to determine whether the perioperative use of dexmedetomidine could reduce the incidence of complications and mortality after cardiac surgery.A total of 1134 patients who underwent coronary artery bypass surgery and coronary artery bypass surgery plus valvular or other procedures were included. Of them, 568 received intravenous dexmedetomidine infusion and 566 did not. Data were adjusted with propensity scores, and multivariate logistic regression was used. The primary outcomes measured included mortality and postoperative major adverse cardiocerebral events (stroke, coma, perioperative myocardial infarction, heart block, or cardiac arrest). Secondary outcomes included renal failure, sepsis, delirium, postoperative ventilation hours, length of hospital stay, and 30-day readmission. Dexmedetomidine use significantly reduced postoperative in-hospital (1.23% versus 4.59%; adjusted odds ratio, 0.34; 95% confidence interval, 0.192-0.614; P<0.0001), 30-day (1.76% versus 5.12%; adjusted odds ratio, 0.39; 95% confidence interval, 0.226-0.655; P<0.0001), and 1-year (3.17% versus 7.95%; adjusted odds ratio, 0.47; 95% confidence interval, 0.312-0.701; P=0.0002) mortality. Perioperative dexmedetomidine therapy also reduced the risk of overall complications (47.18% versus 54.06%; adjusted odds ratio, 0.80; 95% confidence interval, 0.68-0.96; P=0.0136) and delirium (5.46% versus 7.42%; adjusted odds ratio, 0.53; 95% confidence interval, 0.37-0.75; P=0.0030).Perioperative dexmedetomidine use was associated with a decrease in postoperative mortality up to 1 year and decreased incidence of postoperative complications and delirium in patients undergoing cardiac surgery.URL: www.clinicaltrials.gov. Unique identifier: NCT01683448.