Background: Acute renal failure after contrast-induced nephropathy is a clinically important and costly complication after the use of iodine-based contrast media. We investigated the cost and cost-effectiveness of 2 contrast media in patients at high risk of contrast-induced nephropathy. Methods: The analyses were based on a randomized, prospective, multinational clinical study comparing the nephrotoxic effects of an isosmolar nonionic contrast medium, iodixanol, with those of a low-osmolar nonionic contrast medium, iohexol. Resource utilization data were obtained from the study and from a retrospective review of patients' hospital records. Swedish, German, and French unit prices were applied to resources used. Between-group differences in average costs were analyzed using a nonparametric bootstrap method. Results: Resource utilization data for 125 patients were analyzed. Seven contrast media-related serious adverse reactions, of which 6 were acute renal failures, were noted in 6 patients receiving iohexol. Two patients in the iodixanol group had 1 nonserious reaction each. The mean hospitalization cost per patient was €489, €573, and €393 lower after iodixanol than after iohexol using Swedish, German, and French unit prices, respectively. The mean per-patient costs of treating adverse drug reactions were €371, €399, and €445 lower after iodixanol than after iohexol, using the respective unit prices (P = 0.01). Iodixanol was cost-effective compared with iohexol, with both lower costs and better effects related to fewer adverse drug reactions. Conclusions: The isosmolar contrast medium iodixanol appears to be cost-effective when compared with a low-osmolar contrast medium, iohexol, in diabetic patients with renal impairment undergoing angiography. © 2005, Elsevier Inc. All rights reserved.