Objective To evaluate the effectiveness and safety of gabexate mesylate in the prevention of post-endoscopic retrograde cholangiopancreatography （ERCP） pancreatitis （PEP）. Methods The literatures and corresponding references of randomized controlled trials （RCT） on gabexate mesylate in the prevention of PEP were searched from Cochrane library （1970 to December 2010），PubMed （1966 to December 2010），EMBASE （1966 to December 2010），and CBM （1978 to December 2010）.Literature screening，data extraction and methodological quality assessment were individually performed by two researchers.The software RevMan 4.2 of Cochrane Collaboration was used for statistical analysis. Results A total of 11 trails involving 3 012 patients were included. Meta analysis showed that high dose （≥1 000 mg）of gabexate mesylate with slow intravenous infusion （≥12 h） could effectively prevent from PEP （OR=0.27，95%CI： 0.11-0.64, P=0.003） and post-ERCP abdominal pain （OR=0.44，95%CI： 0.25-0.79，P=0.005） when compared with placebo. The low dose （≤500 mg） of gabexate mesylate with quick intravenous infusion （≤6.5 h） could not effectively prevent from PEP （OR=0.85, 95%CI： 0.59-1.34, P=0.570），post-ERCP hyperamylasemia （OR=0.86，95%CI： 0.69-1.07，P=0.180），and post-ERCP abdominal pain （OR=0.66，95%CI： 0.32-1.35，P=0.250）.When compared gabexate mesylate with ulinastatin, there was no statistical difference between them in the prevention of PEP （OR=1.57，95%CI： 0.39-6.24，P=0.520） and post-ERCP hyperamylasemia （OR=1.85, 95%CI： 0.83-4.13，P=0.130）. Conclusions The high dose （≥1 000 mg） of gabexate mesylate with slow intravenous infusion （≥12 h） other than low dose （≤500 mg） with quick intravenous infusion （≤6.5 h） is effective to prevent from PEP and post-ERCP abdominal pain，and can also prevent from post-ERCP hyperamylasemia to some extent.The effect which ulinastatin prevents PEP and post-ERCP hyperamylasemia is same to gabexate mesylate.The above conclusions remain to confirm by RCT with large sample and long-term follow-up of high-quality.