Background The administration of iodinated contrast media is an essential component of many diagnostic and therapeutic procedures that involve radiologic imaging. One important potential side effect of iodinated contrast administration is contrast-induced nephropathy (CIN), defined as an increase in serum creatinine of more than 25 percent or 0.5 mg/dL within 3 days of intravascular administration of contrast media in the absence of an alternative etiology. 1 This definition of CIN is the one most commonly used in the past in studies examining the risk, prevention, and treatment of CIN. More recent definitions of acute kidney injury have not yet been used extensively in the CIN literature. The precise mechanism of CIN is not entirely understood. The leading theories are that CIN results from hypoxic injury of the renal tubules induced by renal vasoconstriction or by direct cytotoxic effects of the contrast media. 2,3 Some experts have questioned whether acute kidney injury occurring after intravascular administration of contrast media is caused by coexisting risk factors and only coincidentally related to the contrast media, especially if contrast media are administered through the intravenous route (IV).4 Regardless of the precise etiology, however, the development of acute kidney injury after use of intravascular contrast media remains a major concern for clinicians. Clinicians often worry about the possibility that intravascular administration of contrast media could lead to acute or chronic kidney failure. The reported incidence of CIN varies, but it is a leading cause of hospital-acquired kidney failure.5 Although renal function returns to normal in most patients, the acute kidney injury may require renal replacement therapy or lead to chronic kidney disease (CKD) in a small proportion of patients who develop CIN. Because of increasing use of contrast media in radiologic and cardiologic procedures, and the increasing prevalence of populations vulnerable to CIN (i.e., people having CKD, diabetes mellitus, or hypertension, as well as the elderly), kidney failure due to CIN is a substantial concern. Numerous strategies have been used to try to prevent CIN. These strategies include oral hydration; volume expansion with sodium chloride or bicarbonate or a combination of both; administration of N-acetylcysteine; withdrawal of metformin, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, or nonsteroidal anti-inflammatory drugs; hemofiltration or hemodialysis; statins; use of low-osmolar or iso-osmolar nonionic contrast media; and reducing the volume of contrast media administered. Despite these varied strategies, no clear consensus exists in clinical practice about the most effective intervention to prevent or reduce CIN. We therefore sought to perform a comprehensive systematic review of the effectiveness of different measures for preventing CIN. We also sought to determine whether the risk of CIN, and therefore the need for preventive measures, varies according to route of administration, type of contrast media, or patient characteristics. Intra-arterial procedures are thought to carry the highest risk of CIN, and therefore most of the studies are in the population undergoing these procedures, while the need for preventive strategies for patients undergoing IV procedures is more controversial. To better understand the results, we separately analyze patients who received IV versus intra-arterial contrast media, as these groups may have different risk profiles and susceptibility to CIN. We also performed a separate analysis for patients receiving iso-osmolar contrast media (IOCM) or low-osmolar contrast media (LOCM), the two types of contrast media in regular clinical use ES-2 today in the United States. Finally, preventive measures may be more effective in patients at higher risk of CIN, so we analyzed data by baseline risk when possible. Key Question In patients undergoing imaging studies requiring intravenous (IV) or intraarterial contrast media, what is the comparative effectiveness of interventions to prevent contrast-induced nephropathy for the outcomes of incidence of contrast-induced nephropathy, chronic kidney disease, end stage renal disease, mortality, and other adverse events? a. How does the comparative effectiveness of prevention measures vary by patient characteristics (known risk factors such as age, comorbidity, glomerular filtration rate, or creatinine level)? b. How does the comparative effectiveness of prevention measures vary according to the type of contrast media used (i.e., low-osmolar contrast media vs. iso-osmolar contrast media)? c. How does the comparative effectiveness of prevention measures vary by characteristics of the interventions (e.g., dose, duration, and timing)? Data Sources We searched the following databases for primary studies published through July 8, 2015: MEDLINE®, Embase®, and the Cochrane Library. In addition, we looked for conference proceedings and other reports by searching the Scopus database. We reviewed the reference lists of relevant articles and related systematic reviews to identify original journal articles and other