Background <p>Cardiac surgery-associated acute kidney injury (CSA-AKI) is a serious perioperative complication for which effective predictive indicators are lacking. This study aimed to investigate the association between the C-reactive protein-triglyceride glucose index (CTI) and CSA-AKI and evaluate its predictive performance. </p> Methods <p>A retrospective analysis was performed on the clinical data of patients who underwent cardiac surgery at Shanghai East Hospital between January 2022 and December 2023. The integrated CTI was calculated as 0.412 × Ln (C-reactive protein) (mg/L) + Ln [triglyceride (mg/dL) × fasting glucose (mg/dL)/2]. Univariate and multivariate logistic regression analyses were used to evaluate the correlation between CTI and CSA-AKI. A restricted cubic spline (RCS) model was applied to assess the nonlinear relationship between CTI and CSA-AKI, while receiver operating characteristic (ROC) curves were utilized to compare the predictive performance of CTI, the triglyceride glucose index (TyG), and C-reactive protein (CRP). Subgroup analyses were conducted to verify the stability of CTI’s predictive value. </p> Results <p>A total of 266 participants were enrolled in our study, including 106 with CSA-AKI and 160 without. CTI exhibited a significant positive nonlinear correlation with the risk of CSA-AKI. The area under the ROC curve (AUC) of CTI for predicting CSA-AKI was 0.772, which was significantly superior to that of TyG (AUC = 0.726) and CRP (AUC = 0.638), with an optimal cutoff value of 9.591. Subgroup analyses further confirmed that the predictive value of CTI for CSA-AKI remained stable across most patient subgroups. </p> Conclusions <p>Elevated CTI levels are associated with an increased risk of CSA-AKI. This study suggests that CTI may represent a potential predictive marker.</p>