Aim: Nephropathy induced by contrast media (CM) still a problem in clinical practice and a variety of therapeutic interventions have been used in an attempt to prevent radiocontrast-induced nephropathy. However most of the published reports are placebo controlled studies and especially in patients with pre-existing renal insufficiency. Therefore, in this study we wanted to investigate and to compare the efficacy of not only one agent, but also N-acetylcysteine, theophylline, nifedipine and misoprostol in the prevention of RCIN in subjects without renal insufficiency. Methods: We studied 97 non-diabetic patients without pre-existing renal insufficiency who received 100 ml low osmolar CM, Iomeprol or Iopamidol. Patients were randomized to five groups; Group S; only saline hydration (SH) used control group, group N; SH plus N-acetylcysteine, group M; SH plus misoprostol, Group N; SH plus nifedipine and Group T; SH plus theophylline. Patients were treated for three days and received 2000 ml saline i.v. each day. Serum creatinine and creatinine clearance were measured before and three days after CM application. Results: We were able to observe RCIN in four patients in group T and one patient in group NAC. Serum creatinine level increased after administration of radiocontrast agent in group M and T. Conclusion: We did not only observe any no additional advantage in administration of N-acetylcysteine (NAC), theophylline, nifedipine and misoprostol to SH alone in the prevention of RCIN but also an adverse effect of theophylline. Therefore, further studies with much more patients were included are necessary.