Purpose: To prospectively compare the protective effect of acetylcysteine, theophylline, and both agents combined in patients who are admitted to the intensive care unit with at least one risk factor for contrast material-induced nephropathy and who receive at least 100 mL of iodinated contrast medium. Materials and Methods: Institutional ethics review board approval and informed consent were obtained. A total of 91 patients (mean age, 58.5 years +/- 14.8 [standard deviation]; 31 women, 60 men; 150 examinations) were admitted to the intensive care unit with at least one risk factor for contrast-induced nephropathy and received either (a) 200 mg theophylline 30 minutes before contrast medium administration (group T), (b) 600 mg acetylcysteine twice daily on the day of and (if possible) the day before the examination (group A), or (c) both agents combined (group AT). The primary end-point for this study was the incidence of contrast-induced nephropathy (x(2) test). Results: Groups T, A, and AT were comparable with regard to baseline creatinine levels and the amount of contrast medium administered. The incidence of contrast-induced nephropathy in groups T, A, and AT was 2%, 12%, and 4%, respectively, and was significantly lower in group T than in group A (P=.047). There was no significant difference in the incidence of contrast-induced nephropathy between groups A and AT (P=.148) or between groups T and AT (P=.53). For group A, serum creatinine did not change after 12, 24, or 48 hours compared with baseline. Creatinine levels in group T decreased 12 hours (1.19 mg/dL +/- 0.58; P=.008) and 48 hours (1.16 mg/dL +/- 0.55; P=.034) after contrast material injection compared with baseline (1.25 mg/dL +/- 0.61). In group AT, creatinine significantly decreased 24 hours (1.21 mg/dL +/- 0.74; P=.003) and 48 hours (1.17 mg/dL +/- 0.69; P=.001) after contrast material injection compared with baseline (1.28 mg/dL +/- 0.74). Group A had significantly higher maximal increases in creatinine than groups T and AT (P