OBJECTIVES: Contrast-induced adverse drug reactions (ADRs), including contrast-induced nephropathy (renal insufficiency and diabetes), are common among high-risk patients (e.g., patients with diabetes mellitus and renal impairment). These ADRs cause extended hospital stays and additional medication use which lead to increased costs. We examine the cost-effectiveness of the use of 2 contrast media in patients at high risk for contrast-induced nephropathy. METHODS: A decision-analytic model was constructed to estimate the cost-effectiveness of an isosmolar contrast agent, iodixanol, compared to a low-osmolar contrast medium, iohexol, in the UK. Particular emphasis of the model was to avert the incidence of severe ADRs in patients at risk of contrast-induced nephropathy. The analysis is based on a European multi-centre randomised controlled trial, the NEPHRIC trial, of patients receiving iodixanol versus ohexol in which a statistically significant reduction in the incidence of severe ADRs in favour of iodixanol occurred. Patients in the study were adults 18 years of age or older referred for coronary or aortofemoral angiography, had diabetes and stable serum creatinine concentrations (men: 1.5 to 3.5 mg/dL; women: 1.3 to 3.5 mg/dL). ADRs considered included acute renal failure, arrhythmia, cardiovascular events, pulmonary edema, and multiple-organ failure. Resource use, including hospital days, medical visits, contrast medium, medications, laboratory tests and hospital procedures, were obtained from the NEPHRIC clinical trial. Unit costs data were obtained from standard UK costing sources. Costs are reported in 2006 £s. RESULTS: Iodixanol is cost-effective compared to iohexol with both lower costs and better effects related to fewer ADRs. The mean per patient cost difference was £555.98 (£0.41 and £556.39for iodixanol and iohexol, respectively). CONCLUSION: Iodixanol results in fewer ADRs and lower ADR costs per patient for this high risk patient population.