ObjectivesThis study aimed to investigate the association between preoperative red blood cell distribution width (RDW) levels and liver injury (LI) after cardiac surgery, to highlight RDW's utility in early identification and intervention for patients at high risk of LI. DesignA retrospective observational study. SettingA university-affiliated teaching hospital and tertiary referral center. ParticipantsAdult patients who underwent cardiac and aortic aneurysm surgery at Changhai Hospital in 2021. InterventionsPostoperative LI was defined by increased liver enzyme levels and/or hyperbilirubinemia, noted from the time of surgery to discharge. Logistic regression analyses were conducted to examine the RDW-LI relationship, with stratified analyses based on age, gender, and anemia. Survival within 30 days was assessed using the Kaplan-Meier method, with survival curve differences analyzed via the log-rank test. The study included three sets of sensitivity analyses. Measurements and Main ResultsPostoperative LI was observed in 75 patients (10%). Multivariate regression analysis showed a significant association between high RDW levels and postoperative LI (adjusted Odds Ratio=3.25, p=0.033, 95% CI:1.1–9.63), even after adjusting for all covariates. This association remained consistent across three sets of sensitivity analyses. Subgroup analysis showed men had a higher correlation with LI (p for interaction=0.041). Kaplan-Meier analysis indicated a significantly lower survival rate in the LI group (76%) compared to the non-LI group (99.6%, P<0.001). ConclusionsPreoperative RDW levels are significantly associated with postoperative LI. RDW could serve as a significant useful marker for early detection and intervention in patients at high risk of LI, thereby potentially improving patient outcomes.