Background: Contrast-induced acute kidney injury (CI-AKI) is one of the possible complications in angiography, which its prevention is important. N-acetylcysteine is one of the compounds that has recently been more investigated regarding its effect on CI-AKI. Objectives: The aim of this study was to investigate the effect of standard dose and twice-thestandard of N-acetyl cysteine on prevention of contrast-induced nephropathy. Patients and Methods: In a clinical trial, 154 individuals who were referred for angiography and had glomerular filtration rate (GFR) ≤60 mL/min, enrolled in and randomly divided into two groups. Group A received the usual dose of N-acetyl cysteine and group B received twice the standard. Blood urea nitrogen (BUN), creatinine, and GFR values were measured and recorded at intervals before, 24, 48 and 72 hours after angiography. Other required laboratory parameters were also measured and recorded. Results: The results of this study indicated that the effect of double dose in males and females is not different. It also has a reverse effect on renal function in older patients. Its effect did not differ in diabetic patients compared to non-diabetic patients. N-acetyl cysteine in dose of twice the standard has not any effect on renal function in patients with hyperlipidemia, hypertension, myocardial infarction, pulmonary edema as well as smoker patients. In patients with congestive heart failure (CHF), N-acetyl cysteine in dose of twice the standard had a positive effect on renal function compared with those who did not have CHF. An interesting point in our study was the negative effect of N-acetyl cysteine in dose of twice-the-standard on renal function in patients with lower hemoglobin and hematocrit levels. Conclusions: Our study showed that an increase in the dose of N-acetyl cysteine is not effective in preventing contrast-induced nephropathy and improving renal function. Of course, in some groups, such as those with CHF, a positive effect was detected. Additionally, in some groups including patients with lower hematocrit and hemoglobin, an increase in dose is associated with a negative effect on renal function. ABSTRACT Implication for health policy/practice/research/medical education:In a clinical trial, on 154 individuals who were referred for angiography or angioplasty and have glomerular filtration rate (GFR) ≤ 60 CC/min showed that an increase in the dose of N-acetyl cysteine is not effective in preventing contrast-induced nephropathy and improving renal function. Please cite this paper as: Eskandarian R, Yarmohamadi M, Zaker-Tavalae M, Mirmohammadkhani M, Biglari M, Tamadon MR, et al. The standard dose versus double dose of N-acetylcysteine to prevent contrast-induced nephropathy; a randomized controlled clinical trial.