Objective: We compared use of intravenous (IV) normal saline (NS) to sodium bicarbonate (NaHCO3) with or without oral N-acetylcysteine (NAC) for prevention of contrast-induced acute kidney injury (CI-AKI). Background: CI-AKI is associated with significant adverse clinical events. Use of NAC has produced variable results. Recently, intravenous hydration with NaHCO3 for CI-AKI prophylaxis has been adopted as standard treatment for patients with stable chronic renal disease undergoing catheterization procedures. Methods: We prospectively enrolled 320 patients with baseline renal insufficiency scheduled to undergo catheterization. Patients were randomly assigned to receive either IV NS ± NAC (n = 161) or IV dextrose 5% in water containing 154 mEq/l of NaHCO3 ± NAC (n = 159). IV NS was administered at 1 ml/kg body weight for 12 hr preprocedure and 12 more hr postprocedure. IV NaHCO3 was administered at 3 ml/kg body weight for 1 hr preprocedure followed by 1 ml/kg body weight postprocedure. A 1,200 mg oral dose of NAC was given 2–12 hr preprocedure and 6–12 hr postprocedure in 50% of patients in each study arm. CI-AKI was defined as an increase of >0.5 mg/dl or >25% above baseline creatinine. Results: Overall incidence of CI-AKI was 10.3%. There was no significant difference in incidence among the two groups (NS ± NAC 11.8% vs. NaHCO3 ± NAC 8.8%, p = ns). Incidence of CI-AKI increased with increasing age (p = 0.001), contrast agent use >3 ml/kg body weight (p = 0.038) and diuretic use (p = 0.005). Conclusion: Incidence of CI-AKI was no different in the NaHCO3 group compared to NS group, and NAC did not reduce CI-AKI in the two study arms. © 2011 Wiley Periodicals, Inc.