Objective: To explore the risk factors for progression to chronic kidney disease (CKD) in patients with cardiac valve replacement surgery-associated acute kidney injury (AKI). Methods: A retrospective, nested case-control study was conducted at Fuwai Central China Cardiovascular Hospital. The study subjects were patients who underwent cardiac valve replacement surgery from January 1, 2018 to December 31, 2020, with a baseline estimated glomerular filtration rate (eGFR)>60 ml·min-1·(1.73 m2)-1 and postoperative complication of AKI. The patients were followed up for 90 days after discharge from hospital. The endpoint event was defined as progression to CKD 90 days after the occurrence of cardiac valve replacement surgery-associated AKI. The patients were divided into CKD group and non-CKD group based on whether they experienced endpoint event. The baseline clinical data were compared between the two groups. The measurement data with non-normal distribution was represented as M (Q1,Q3). Logistic regression model was used to analyze the risk factors of endpoint event. The receiver-operating characteristic (ROC) curve was drawn to evaluate the performance for predicting CKD in cardiac valve replacement surgery-associated AKI patients. Results: A total of 149 cardiac valve replacement surgery-associated AKI patients (86 males and 63 females) were included in the study, aged (59.0±10.2) years. There were 27 patients (18.1%) who progressed to new-onset CKD 90 days after the occurrence of cardiac valve replacement surgery-associated AKI. Compared with non-CKD group, patients in CKD group had older age [66 (58, 70) vs 59 (53, 64) years], lower baseline eGFR [76.3 (65.8, 98.5) vs 92.7 (78.5, 101.6) ml·min-1·(1.73 m2)-1], higher proportion of preoperative hypertension [51.9% (14/27) vs 27.9% (34/122)] and serum creatinine at discharge [136 (101, 165) vs 86 (65, 104) μmol/L], and the differences were statistically significant (all P<0.05). The multivariate logistic regression analysis results revealed that older age (OR=1.063, 95%CI: 1.001-1.129, P=0.047), preoperative hypertension (OR=3.070, 95%CI: 1.105-8.532, P=0.031) and higher serum creatinine at discharge (OR=1.026, 95%CI:1.013-1.038, P<0.001) were risk factors for progression to CKD in patients with cardiac valve replacement surgery-associated AKI. The clinical risk model including age, preoperative hypertension, preoperative baseline eGFR, and serum creatinine at discharge produced a moderate performance for predicting progression to CKD in patients with cardiac valve replacement surgery-associated AKI [the area under the curve (AUC)=0.865, 95%CI: 0.790-0.940, P<0.001]. Conclusion: Older age, preoperative hypertension and higher serum creatinine at discharge are risk factors for progression to CKD in patients with cardiac valve replacement surgery-associated AKI.