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OBJECTIVE Mechanisms and consequences of late-onset hyperlactatemia after cardiac surgery remain unclear. The aim of this study was to identify risk factors and outcomes of late hyperlactatemia, defined as a lactate value ≥3 mmol/L developing in the intensive care unit (ICU) after not being elevated on admission after cardiac surgery with cardiopulmonary bypass. DESIGN A retrospective analysis of prospectively collected data. SETTING A single-center University Hospital. PARTICIPANTS Patients who underwent elective cardiac surgery with cardiopulmonary bypass in 2019 and who had normal lactatemia at ICU admission. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Patients were divided in 2 groups according to their lactatemia on postoperative day 1 (14.0 ± 3.0 hours after ICU admission): normal lactatemia (control group) and late hyperlactatemia (HL group). Risk factors for late hyperlactatemia were identified using a multivariate analysis, and postoperative outcomes were compared using a composite criterion of severe outcomes. Of the 432 included patients, 37 (8.5%) presented with late hyperlactatemia. Risk factors independently associated with hyperlactatemia were afternoon surgery (odds ratio [OR] 4.24, 95% CI 2.00-9.35), a bleeding >300 mL within the 6 hours after surgery (H6) (OR 3.77, 95% CI 1.71-8.30), and H6 fluid loading >250 mL (OR 2.64, 95% CI 1.22-5.55). Patients with hyperlactatemia presented more frequently with major postoperative complications, including acute kidney injury, and received more frequent red-cell transfusion. CONCLUSION The strongest risk factors associated with late-onset hyperlactatemia in the authors' population were afternoon surgery and H6 bleeding >300 mL. Poor postoperative outcomes were more frequent in patients with late hyperlactatemia, even in the absence of early hyperlactatemia or severe obvious condition.