Reactive oxygen species play a major role in the pathogenesis of contrast-induced nephropathy (CN). Hydration with sodium bicarbonate (HCO ₃ ⁻ ) can reduce the incidence of CN in high-risk patients, suggesting a direct causal relationship between low pH of tubular fluid and enhanced activity of generated reactive oxygen species to damage renal tubular cells. Whether acetazolamide (AZ), a carbonic anhydrase inhibitor, is more effective than HCO ₃ ⁻ unknown. Ninety-six children with stable chronic renal insufficiency were randomly assigned to receive either a 154 mEq/L infusion of sodium bicarbonate (HCO ₃ ⁻ ) (n = 46) or 0.9% sodium chloride plus oral AZ (n = 50) at a rate of 3 ml/kg/hr for 1 hour before and 1 ml/kg/hr for 6 hours after the radiographic procedure. Serum creatinine concentration (Scr) was measured before and 48 hours after the procedure. The primary endpoint was an increase in the Scr concentration of ≥25% 48 hours after the contrast administration. The baseline clinical and biochemical characteristics of the two groups were similar. The mean Scr concentration after contrast administration was significantly lower in the AZ group (p = 0.02) than in the HCO ₃ ⁻ group (p = 0.27). The mean absolute decrease in Scr concentration at 48 hours was significantly greater in the AZ group (p < 0.01). Four of the 46 patients (8.7%) in the HCO ₃ ⁻ group had an increase in the Scr concentration of ≥25% compared with none of the 50 patients (0%) in the AZ group (p = 0.049). Thus, compared to HCO ₃ ⁻ , AZ plus saline hydration was more effective for the prevention CN after radiographic procedure.