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Background/Objectives: Hyperlactatemia is a common predictive factor for poor post-cardiovascular surgery outcomes. However, it is not well understood whether the rapid postoperative lactate level elevation in a short period of time is associated with patient outcomes. Herein, we investigated the relationship between the degree of change in serum lactate levels and postoperative serious adverse events (PSAEs), including mortality, within 24 h of cardiovascular surgery. Methods: In this retrospective study, we evaluated the relationship between a rapid serum lactate level increase and PSAEs after open-heart and major vascular surgery. We divided the patients into those with and without PSAEs. Univariate and multivariate analyses were performed to evaluate the association between PSAEs and rapid lactate level increases. Results: We enrolled 445 patients; 16% (n = 71) had PSAEs. The peak lactate levels during the first 24 h of intensive care unit (ICU) stay were higher in patients with PSAEs than in those without. The maximum change in lactate levels between two consecutive lactate measurements during the first 24 h after ICU admission was higher in patients with PSAEs than in those without. A multivariate logistic regression analysis revealed that changes in lactate levels of 2 mmol/L or more between two consecutive lactate measurements were associated with PSAEs. ICU peak lactate levels of 3 mmol/L or more were not associated with PSAEs. Conclusions: Rapid serum lactate level increases of 2 mmol/L or more during the first 24 h of ICU admission post-cardiovascular surgery are associated with PSAEs. Full article