Introduction Postoperative acute kidney injury (AKI) following arthroplasty has not been well studied. Our aim was to identify factors associated with increased risk of AKI. Methods The medical records for adult patients who underwent elective total joint arthroplasty during June 1, 2007 to May 31, 2010 at the Mayo Clinic were reviewed to identify patients with normal preoperative kidney function who experienced perioperative AKI, defined as an increase in serum creatinine (sCr) by 26.4 lmolÁL -1 . For each AKI case, two controls were identified and matched for age, sex, and type of operation. Medical records were abstracted for demographics, comorbid conditions, and preoperative, intraoperative, and postoperative variables. Conditional logistic regression analyses were performed to identify risk factors for AKI. Results Of the 9,171 patients who underwent joint replacement operations, 167 with normal preoperative renal function developed AKI with a median [25 th , 75 th ] increase in sCr of 35.4 [26.4, 44.2] lmolÁL -1 . No patient required dialysis. A higher than normal body mass index, diabetes mellitus, the number of baseline antihypertensive medications, cerebral or peripheral vascular disease, use of general anesthesia, and perioperative blood transfusions were independently associated with risk for AKI. Hospital length of stay and intensive care admissions were greater in AKI patients, and in 12.0% of patients, sCr remained at least 26.4 lmolÁL -1 higher than preoperative baseline at least three months after surgery. Conclusion In this case-control investigation, we identified several factors associated with the development of postoperative AKI. Recognition of these risk factors could allow for the adoption of perioperative renal protective strategies in patients undergoing arthroplasty.