Acute kidney injury (AKI) is a serious complication of cardiovascular surgery. Although some nonexperimental studies suggest that statin use may reduce postsurgical AKI, methodologic differences in study designs leave uncertainty regarding the reality or magnitude of the effect. The aim of this study was to estimate the effect of preoperative statin initiation on AKI after coronary artery bypass grafting (CABG) using an epidemiologic approach more closely simulating a randomized controlled trial in a large CABG patient population. Health care claims from large, employer-based and Medicare insurance databases for 2000 to 2010 were used. To minimize healthy user bias, patients were identified who underwent nonemergent CABG who either newly initiated a statin <20 days before surgery or were unexposed for ≥200 days before CABG. AKI was identified <15 days after CABG. Multivariate-adjusted risk ratios (RRs) and 95% confidence intervals (CIs) were calculated using Poisson regression. Analyses were repeated using propensity score methods adjusted for clinical and health care utilization variables. A total of 17,077 CABG patients were identified. Post-CABG AKI developed in 3.4% of statin initiators and 6.2% of noninitiators. After adjustment, a protective effect of statin initiation on AKI was observed (RR 0.78, 95% CI 0.63 to 0.96). This effect differed by age, with an RR of 0.91 (95% CI 0.68 to 1.20) for patients aged ≥65 years and an RR of 0.62 (95% CI 0.45 to 0.86) for those aged <65 years, although AKI was more common in the older group (7.7% vs 4.0%). In conclusion, statin initiation immediately before CABG may modestly reduce the risk for postoperative AKI, particularly in younger CABG patients.