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Inotropes used to obtain short-term hemodynamic benefits in cardiac surgery may carry a risk of increased myocardial ischemia and adverse outcomes. This study investigated the association between intra- and postoperative use of inotropes and mortality and postoperative complications.A historic cohort study using prospective data from the Western Denmark Heart Registry on 6,005 consecutive cardiac surgery cases from three university hospitals. Propensity matching on pre- and intraoperative variables was used to identify a subgroup of patients receiving inotropic therapy (n = 1,170) versus comparable nonreceivers (n = 1,170) for outcome analysis.Two thousand ninety-seven patients (35%) received inotropic therapy; 3,908 (65%) did not receive any inotropic or vasopressor support perioperatively. Among propensity-matched cohort including 2,340 patients 30-day mortality was 3.2% and 1-yr mortality was 7.6%. In the matched cohort, patients exposed to inotropes had a higher 30-day mortality (adjusted hazards ratio, 3.7; 95% CI, 2.1 to 6.5) as well as a higher 1-yr mortality rate (adjusted hazards ratio, 2.5; 95% CI, 1.8 to 3.5) compared with nonreceivers. Among propensity-matched, the following absolute events rates were observed: myocardial infarction 2.4%, stroke 2.8%, arrhythmia 35%, and renal replacement therapy 23.9%. Inotropic therapy was independently associated with postoperative myocardial infarction (adjusted odds ratio, 2.1; 95% CI, 1.4 to 3.0), stroke (adjusted odds ratio, 2.4; 95% CI, 1.4 to 4.3), and renal replacement therapy (adjusted odds ratio, 7.9; 95% CI, 3.8 to 16.4).Use of intra- and postoperative inotropes was associated with increased mortality and major postoperative morbidity.