ERCP is attended with certain complications, the majority of which are well known to the medical community. Other less-known complications also exist. Guidewire injury to the hepatic or pancreatic parenchyma represents one of the much less appreciated, albeit preventable, complications. In this report, we present the clinical course of three patients who sustained guidewire perforation of the pancreatic or hepatic parenchyma. In one patient, the clinical deterioration was confidently attributed to guidewire perforation of the pancreatic parenchyma. Conservative treatment was successful and unnecessary emergency surgery was thus avoided. In the other two, in whom the cause of the clinical deterioration was unclear, an emergency surgery was performed. Guidewire injury to the hepatic parenchyma was then confirmed which needed only intraperitoneal drainage, with successful outcome.