Objective To investigate the clinical effect of ulinastatin in preventing pancreatitis after endoscopic retrograde cholangiopancreatography( ERCP). Methods The Cochrane Library,Pub Med,EMBASE,CNKI,VIP,and Wanfang Data were searched for randomized controlled trials( RCTs) on ulinastatin for the prevention of post- ERCP pancreatitis published from 1970 to June 2016. Two researchers selected RCTs,extracted data,and evaluated methodological quality independently,and Rev Man 5. 3 software was used for the meta- analysis. The chi- square test was used for the heterogeneity analysis of RCTs included,and the funnel plots were used to evaluate publication bias. Results A total of six RCTs with 923 patients were included in this analysis. Compared with the placebo,ulinastatin had significantly better effects in preventing post- ERCP pancreatitis( OR = 0. 26,95% CI: 0. 13- 0. 53,P = 0. 000 2),hyperamylasemia( OR = 0. 47,95% CI: 0. 33- 0. 67,P 0. 001),and abdominal pain( OR = 0. 56,95% CI: 0. 34- 0. 91,P = 0. 020). Compared with gabexate,ulinastatin had similar effects in preventing post- ERCP pancreatitis,hyperamylasemia,and abdominal pain( P = 0. 52,0. 13,and 0. 79); low- dose ulinastatin also had similar effects as gabexate in preventing post- ERCP pancreatitis and hyperamylasemia( P = 0. 49 and0. 25). The funnel plots based on the effect of ulinastatin in preventing post- ERCP pancreatitis were slightly asymmetric,which suggested the presence of publication bias. Conclusion Ulinastatin( > or =15 x 104U) can effectively prevent post- ERCP pancreatitis,hyperlipidemia,and abdominal pain in the general population and it is recommended to start using this drug before surgery.