Various factors have been shown to be associated with the development of post-ERCP pancreatitis. They are generally classified as patient-related factors and procedure-related factors. These factors exert a synergistic effect on the risk for pancreatitis after ERCP. The pathogenesis of post-ERCP pancreatitis has not been fully understood, but several factors (i.e., mechanical injury, hydrostatic injury, chemical and allergic injury, enzymatic injury, infection, and thermal injury) may act independently or in combination to provoke post-ERCP pancreatitis. Since the introduction of ERCP, numerous pharmacologic agents have been evaluated to prevent post-ERCP pancreatitis on the assumption that they pharmacologically inhibit one or more of the factors associated with pancreatic damage. Pancreatitis is the most common and feared complication of ERCP. Identification of risk factors before and during ERCP is of paramount importance. The benefit of performing ERCP should be outweighed by the risk of post-ERCP pancreatitis.