Background: Pancreatitis is the most common major complication of diagnostic a nd therapeutic ERCP. Allopurinol,a xanthine oxidase inhibitor that blocks genera tion of oxygen-derived free radicals, potentially may prevent post-ERCP pancre atitis. This study assessed the efficacy of high-dose oral allopurinol for prev ention of post-ERCP pancreatitis. Methods:A prospective, double-blind, placebo -controlled trial was conducted in 250 patients undergoing ERCP. Patients were randomized to receive allopurinol (600 mg) or placebo orally at 15 and 3 hours b efore the procedure. Patients were clinically evaluated, and serum amylase level s were determined before ERCP and at 6 and 24 hours thereafter. Standardized cri teria were used to diagnose and to grade the severity of post-ERCP pancreatitis . Results: A total of 243 patients were included in the analysis. The two groups were similar with regard to age;gender; underlying disease; indication for trea tment; ERCP findings; and type of treatment, except for biliary sphincterotomy.O nly 43 patients in the allopurinol group underwent biliary sphincterotomy vs. 87 in the placebo group (p< 0.001).The frequency of acute pancreatitis was signifi cantly lower in the allopurinol vs. the placebo group in the final multinomial r egression analysis: allopurinol group, 4/125 (3.2%), with all 4 cases graded as mild, vs. placebo group, 21/118 (17.8%),of which 8/118 (6.8%) were graded as mild, 11/118 (9.3%) as moderate, and 2/118 (1.6%) as severe with fatal outcome (p< 0.001). The protective effect of allopurinol was also apparent in the diagn ostic ERCP and the biliary sphincterotomy subgroups when the frequency of post- ERCP pancreatitis was analyzed after stratification by procedure. The mean durat ion of hospitalization for pancreatitis was significantly shorter in the allopur inol compared with the placebo group (2.5 vs. 5.67 days;p < 0.001). Conclusions: Pretreatment with high-dose, orally administered allopurinol decreases the fre quency of post-ERCP pancreatitis. Despite the promising results of this prospec tive,randomized trial, further studies are needed to verify these observations b efore allopurinol can be recommended for routine clinical use. Background: Pancreatitis is the most common major complication of diagnostic a nd therapeutic ERCP. Allopurinol, a xanthine oxidase inhibitor that blocks genera tion of oxygen-derived free radicals, potentially may prevent post-ERCP pancre atitis. This study assessed the efficacy of high- dose oral allopurinol for prev ention of post-ERCP pancreatitis. Methods: A prospective, double-blind, placebo-controlled trial was conducted in 250 patients undergoing ERCP. Patients were randomized to receive allopurinol (600 mg) or placebo orally at 15 and 3 hours b efore the procedure. Patients were clinically evaluated, and serum amylase levels were determined before ERCP and at 6 and 24 hours thereafter. Standardized cri teria were used to diagnose and to grade the severity of post-ERCP pancreatitis. Results: A total of 243 patients were included in the analysis. The two groups were similar with regard to age; gender; underlying disease; indication for trea tment; ERCP findings; and type of treat ment, except for biliary sphincterotomy. Of 43 patients in the allopurinol group underwent biliary sphincterotomy vs. 87 in the placebo group (p <0.001). The frequency of acute pancreatitis was signifi cantly lower in the allopurinol vs. the placebo group in the final multinomial r egression analysis: allopurinol group, 4/125 (3.2%), with all 4 cases graded as mild, vs. placebo group, 21/118 (17.8%), of which 8/118 (6.8%) were graded as mild, 11/118 (9.3%) as moderate, and 2/118 (1.6%) as severe with fatal outcome (p <0.001). The protective effect of allopurinol was also apparent in the diagnostic ERCP and the biliary sphincterotomy subgroups when the frequency of post-ERCP pancreatitis was analyzed after stratification by procedure. The mean durat ion of hospitalization for pancreatitis was significantly shorter in the allopur inol compared with the placebo group (2.5 vs. 5.67 days; p <0.001). Conclusions: Pretreatment with high-dose, orally administered allopurinol decreases the frDespite the promising results of this prospecive tive, randomized trial, further studies are needed to verify these observations b efore allopurinol can be recommended for routine clinical use.