The impact of preoperative statin use on postoperative acute kidney injury (AKI) is uncertain. We aimed to examine the association of statin therapy before cardiac surgery with postoperative AKI. The retrospective cohort study consisted of 1581 patients undergoing cardiac surgery. Postoperative AKI were identified by the modified KDIGO definition. Propensity-score matching was employed to control for selection bias, and logistic regression was used to control for confounders. Subgroup and interaction analyses were performed to evaluate the robustness of the findings. The overall incidence of postoperative AKI and severe AKI were 42.19% and 12.27%, respectively. Preoperative moderate-dose statin was significantly associated with a reduced incidence of postoperative AKI (28.9% vs 43.0%, OR (95%CI): 0.54 (0.38, 0.77), p < 0.001) and severe AKI (6.9% vs 13.7%, OR (95%CI): 0.46 (0.26, 0.83), p = 0.009). The beneficial effect on postoperative AKI persisted after adjusting for major confounding factors (OR (95%CI): 0.47 (0.34, 0.66)). Decreased risk of postoperative AKI was observed in patients with preoperative statin duration of 7 ∼ 14 days (OR (95%CI): 0.41 (0.25, 0.65)) and over 14 days (OR (95%CI): 0.43 (0.28, 0.65)), but not in those with preoperative statin duration of <7 days. Similar favorable effects were noted in most subgroup patients, except for those with high-risk factors such as diabetes mellitus, previous congestive cardiac failure, arrhythmia, preoperative ACEI/ARB, aortic cross-clamping or IABP. Preoperative moderate-dose statin was significantly related to a decreased risk of postoperative AKI, especially in patients who received statins for a longer duration. Further large-scale multicenter randomized controlled trials are needed to ascertain the impact of statin dose, duration, and timing on postoperative AKI in cardiac surgery patients. [ABSTRACT FROM AUTHOR]