The use of radiographic contrast during cardiac catheterization can cause acute renal failure with an increase in morbidity and mortality. Prophylactic acetylcysteine plus intravenous hydration have been shown to prevent contrast-induced nephropathy (CIN) in patients with chronic renal failure undergoing computed tomography scan, who receive low doses of intravenous contrast. Whether the use of prophylactic acetylcysteine can decrease the incidence of CIN when larger doses of contrast are used remains to be determined. We sought to evaluate whether the prophylactic administration of acetylcysteine plus intravenous hydration is superior to intravenous hydration alone in prevention of CIN in patients with chronic renal failure undergoing cardiac catheterization and receiving moderate to high doses of intravenous contrast (> 1 cc/kg). Seventy-three consecutive patients with renal insufficiency who received intravenous hydration and 600 mg of acetylcysteine twice a day 24 hr before and the day of the cardiac catheterization were compared with 106 consecutive patients who received hydration alone. Baseline and 48-hr serum creatinine concentrations were compared between the two groups before and after cardiac catheterization. Multivariate and univariate analysis were performed to assess the effects of acetylcysteine and other clinical variables in the change of serum creatinine after the procedure. Both groups had comparable clinical characteristics and received similar volumes of intravenous hydration. The volume of contrast used was similar for the two groups (2.2 +/- 1.7 vs. 2.3 +/- 1.5 cc/kg; P = 0.67). A mean change in serum creatinine of 0.17 +/- 0.54 mg/dl for the acetylcysteine group vs. 0.19 +/- 0.40 mg/dl for the control group (P = 0.77) was observed at 48 hr. The incidence CIN was 13% in the acetylcysteine vs. 12% in the control group (P = 0.84). Acetylcysteine, whether analyzed with multivariate or univariate analysis, failed to demonstrate a significant effect in the change of serum creatinine after cardiac catheterization. In patients with chronic renal insufficiency, acetylcysteine in a dose of 600 mg twice a day before and after cardiac catheterization, along with intravenous fluids, is as effective as fluids alone in the prevention of CIN when moderate to high doses of contrast are used.