Presently, only hydration and N-acetylcysteine have been shown to be effective in decreasing the incidence of radiographic contrast-induced nephropathy. We investigated the role of N-acetylcysteine and various hydration protocols in vascular surgery patients undergoing angiography. A single-center, randomized, placebo-controlled trial was conducted in patients with stable, preexisting renal dysfunction undergoing elective, outpatient angiography. Patients were randomized to outpatient oral hydration and N-acetylcysteine, inpatient hydration plus N-acetylcysteine, or our standard therapy of inpatient intravenous hydration alone. Two of twenty-eight (7%) patients who received outpatient oral hydration and N-acetylcysteine developed contrast-induced nephropathy, while two of 25 (8%) who recieved inpatient hydration plus N-acetylcysteine developed contrast-induced nephropathy and two of 25 (8%) who received standard therapy of inpatient intravenous hydration alone developed contrast-induced nephropathy. There was no statistical difference in incidence of contrast-induced nephropathy between the groups. No statistically significant independent risk factors were identified among the patients who developed contrast-induced nephropathy. N-Acetylcysteine did not confer additional benefit to patients treated with inpatient intravenous hydration. Outpatient oral hydration plus N-acetylcysteine was as effective at preventing contrast-induced nephropathy as inpatient therapies and avoided costly hospital admission.