Background: We conducted the following study to analyze the risk factors of postoperative acute kidney injury (AKI) in patients diagnosed with infectious endocarditis (IE) and their impact on outcomes. Methods: We retrospectively analyzed patients with IE treated surgically. We use a contingency table method and logistic regression analysis for investigation of the relationship with perioperative risk factors, Kaplan Meier analysis for survival rate, logarithmic rank test for inter group survival rate differences, Spearman analysis for the correlation of two variates, receiver operating characteristic (ROC) analysis for the diagnostic value of risk factors, and the Youden index for the optimal value. Results: 848 patients were enrolled and divided into a group with AKI (n = 272) and a group without AKI (n = 576). The incidence of postoperative AKI was 32.1% (272/848). Male gender (p < 0.001), preoperative aortic regurgitation (p < 0.001), paravalvular leak (p < 0.001), cardiopulmonary bypass length ≥120 minutes (p < 0.001), aortic occlusion duration ≥90 minutes (p < 0.001), mechanical ventilation length ≥72 hours (p < 0.001), contrast iodine (p = 0.048), and vancomycin (p < 0.001) were found to be risk factors of postoperative AKI in IE. A positive relationship exists between cardiopulmonary bypass length and postoperative AKI (r = 0.406, p < 0.001). A value of cardiopulmonary bypass length >161 minutes was 70.6% sensitive and 83.3% specific for the diagnosis of postoperative AKI (p < 0.001). Long-term survival in the group with AKI was significantly less than that in the group without AKI. Conclusions: Postoperative AKI in IE contributes to an apparent increase in in-hospital and long-term mortality. Optimization of the management of AKI will improve the short- and long-term outcomes of postoperative an AKI in IE.