The contrast-induced nephropathy (CIN) is the third most common cause of acute renal failure (ARF) and the worsening in a pre-existing chronic renal failure (CRF), with a foreseeable increase of morbidity, mortality, length of the stay in hospital and, as a consequence, of the health costs. We studied the effectiveness of N-acetylcysteine (NAC) associated with sodium bicarbonate (Na2HCO3) infusion in order to prevent CIN in patients undergoing coronary angiography with administration of contrast medium. 296 patients with indication to perform coronary angiography were included in a randomized, observational study. All patients were randomly assigned to receive pre- and post-contrast hydration with 1500 ml of 0.9% saline solution infusion (Group A) or NAC (1200 mg × 2 days) + Na2HCO3 (Group B). The primary end-point was to examine CIN appearance, defined as a raise in serum values of Cr (Creatinine) ≥ 0.5 mg/dl or ≥ 25% within 24-72 hours after the exposure to the contrast medium. It has been observed a frequency of CIN of 9.4% in Gr. A compared to 7.2% in Gr. B. Nevertheless, when we put these results through a more accurate screening according to gender, degree of raise in creatinine levels and the extent of change in GFR (glomerular filtration rate), we observed a very different behaviour. In patients with normal Cr and CrCl (Clearance of Creatinine) the frequency of CIN was similar in both group A and B (approximately 5%). In patients with normal Cr but reduced ClCr the use of NAC was more effective than hydration in preventing CIN (0% vs 18% in prevalence respectively in B and A group). In patients with moderately reduced Cr and CrCl, hydration with saline solution was more effective than NAC + Na2HCO3 (8.6% vs 17.6%) while in patients with severe CRF the combined use of NAC + Na2HCO3 showed off to be very successful in preventing CIN compared to the merely hydration (0% vs 50%). In patients affected by severe CRF who are undergoing investigations with contrast medium administration, such as coronary angiography, the combined use of NAC + Na2HCO3 infusion significantly reduces the risk of developing CIN. In other circumstances the final result is related to the degree of previous GFR or creatinine values alteration or to gender. In such situations the combined use of both substances is more questionable and sometimes ineffective.