Enhanced production and reduced removal of oxygen free radicals may play an important role in the pathogenesis of the contrast-induced acute kidney injury (CIAKI). Probucol, a lipid-lowering drug with potent antioxidant properties, has been widely used clinically for the prevention of the progression of atherosclerosis. We performed a prospective, randomized controlled trial to investigate the role of probucol in the prevention of CIAKI in patients undergoing planned coronary angiography (CAG) or intervention. The 205 patients who underwent planned CAG or intervention were randomly assigned to either the probucol group (n = 102; 500 mg orally twice daily) or the control group (n = 103). Renal function was assessed at the time of hospital admission and on days 1, 2, and 3 after the procedure. CIAKI occurred in 23 (11.22%) of the 205 patients. The incidence of CIAKI in the probucol group was slightly lower compared with the control group (7.84% vs 14.56%) but without significant difference (p = 0.13). The postprocedure mean peak of serum creatinine (1.15 +/- 0.49 vs 1.33 +/- 0.78 mg/dl, p = 0.04) and the postprocedure increasing Scr from baseline (0.15 +/- 0.22 vs 0.25 +/- 0.21 mg/dl, p = 0.001) in the probucol group were significantly lower than those in the control group. In conclusion, prophylactic treatment with probucol during the periprocedural stage in patients undergoing coronary angiography or intervention has a preventive role against CIAKI.