Objective: Contrast nephropathy is the cause of 5% to 30% of in patients with acute renal failure. Although recovery is high, but may need dialysis in 10% to 25% of cases and increase the duration of admission and increase mortality by five folds. The aim of this study was to assess the role of N-acetyl-cysteine (NAC) as an antioxidant agent, in prevention of radio contrast- induced nephropathy in high risk patients among candidate for angiography in Golestan hospital in Ahwaz, Iran.Subjects and Methods: One hundred patients, who had at least one of the following risk factors: age >60 years, diabetes mellitus, heart failure (ejection fraction <35%) or renal insufficiency (creatinine³1.5mg/dl), were studied. Fifty patients who were administered NAC (600mg twice a day orally plus 1 litre of normal saline, the day before and again after angiography) were compared with 50 patients who received only normal saline. Angiography was done by Omnipaque or Ultravist contrast media. Before and 48 hours after angiography, serum creatinine, was determined. Radio-contrast-induced nephropathy was defined as an increase increment of creatinine level of more than 0.5mg/dl.Results: The patients were 40-78 years old, 58 patients were male and 42 were female. Diabetes mellitus was recognized in 36% of patients, CHF in 16%, renal insufficiency in 25% and age >60 years in 23%. Contrast nephropathy occurred in 5 patients of control group (2 of them had diabetes mellitus, 2 had renal insufficiency and one was age >60 years), but -no one in NAC. The difference in two groups was significant (p< 0.05). In NAC group, mean of serum creatinine level decreased 0.08mg/dl but in controls, increased 0.16mg/dl (p< 0.05). NAC had no side effects in patients.Conclusion: The incidence of radio-contrast-induced nephropathy in the NAC group was significantly lower than in the control group. NAC is a safe and effective agent in prevention of radio-contrast-induced nephropathy in high risk patients