Background: Selective intrahepatic ductal cannulation during ERCP remains difficult, particularly when strictures involve the bifurcation and/or secondary intrahepatic branches. Methods: A retrospective review was conducted of a cohort of 16 patients (stones 5, cholangiocarcinoma 5, primary sclerosing cholangitis 4, hepatoma 1, bile leak 1) in whom selective cannulation of the intrahepatic ducts with conventional techniques was unsuccessful and who underwent ERCP with a sphincterotome and a hydrophilic coated guidewire to achieve intrahepatic ductal access. Results: The procedure was technically successful in 15 patients and clinically successful in 12. In the 5 patients with bile duct stones, clearance was obtained in 3 and stents were placed in the other 2 patients; one died of cholangitis within 30 days and the other underwent surgery. The procedure was technically successful in 3 of the 5 patients with cholangiocarcinoma. One patient died and the procedure was technically unsuccessful in another. For all patients with primary sclerosing cholangitis, the endoscopic therapy was technically successful and clinical outcomes satisfactory. The patient with a hepatoma was treated successfully and subsequently died of hepatic failure. Conclusion: Use of a sphincterotome and hydrophilic-coated guidewire can significantly enhance the success rate for selective intrahepatic ductal access.