Pancreatitis remains the most common and potentially fatal complication following ERCP. Various pharmacological agents have been used in an attempt to prevent post-ERCP pancreatitis, but most randomized controlled trials have failed to demonstrate their efficacy. Antiproteases, which have been clinically used to manage acute pancreatitis, would theoretically reduce pancreatic injury after ERCP because activation of proteolytic enzymes is considered to play an important role in the pathogenesis of post-ERCP pancreatitis. Gabexate and ulinastatin have recently been evaluated regarding their efficacy in preventing post-ERCP pancreatitis. Long-term (12 hours) infusion of gabexate significantly decreased the incidence of post-ERCP pancreatitis; however, no prophylactic effect was observed for short-term infusion (2.5 and 6.5 hours). These results may be due to the short-life of gabexate (55 seconds). Since long-term infusion requires additional hospitalization, the use of gabexate in all patients at average risk of developing post-ERCP pancreatitis is an expensive strategy. Ulinastatin has a half-life of 35 minutes and can be given as a bolus infusion. Short-term (10 minutes) administration of ulinastatin showed a significant reduction in the incidence of post-ERCP pancreatitis in one randomized controlled trial. Ulinastatin is superior to gabexate in terms of cost because it does not require additional hospitalization. At present, there is no other randomized, placebo-controlled trial on ulinastatin under way. Large scale randomized controlled trials revealed that both the long-term infusion of gabexate and the short-term administration of ulinastatin may reduce pancreatic injury, but these studies involve patients at average risk of developing post-ERCP pancreatitis. Additional research is needed to confirm the preventive efficacy of these antiproteases in patients at a high risk of developing post-ERCP pancreatitis.